Pub Date : 2020-12-31eCollection Date: 2020-01-01DOI: 10.1155/2020/6694214
Yujing Xia, Jingjing Li, Kan Chen, Jiao Feng, Chuanyong Guo
Liver fibrosis is a pathological process involving diffuse extracellular matrix (ECM) deposition in the liver. It is typical of many chronic liver diseases, including cirrhosis, and effective drugs are needed. In this study, we explored the protective effect of bergenin on liver fibrosis induced by carbon tetrachloride and bile duct ligation. A variety of molecular biological methods (qRT-PCR, western blotting, and immunohistochemistry) were employed to confirm the increased degree of hepatocyte injury and ECM formation in the disease model, consistent with autophagy and activation of the TGF-β pathway. Bergenin activated PPAR-γ and inhibited TGF-β and autophagy and decreased liver fibrosis by inhibiting hepatocyte necrosis and ECM formation in a dose-dependent manner. The results suggest that bergenin may be a promising drug candidate for the treatment of liver fibrosis.
{"title":"Bergenin Attenuates Hepatic Fibrosis by Regulating Autophagy Mediated by the PPAR-<i>γ</i>/TGF-<i>β</i> Pathway.","authors":"Yujing Xia, Jingjing Li, Kan Chen, Jiao Feng, Chuanyong Guo","doi":"10.1155/2020/6694214","DOIUrl":"https://doi.org/10.1155/2020/6694214","url":null,"abstract":"<p><p>Liver fibrosis is a pathological process involving diffuse extracellular matrix (ECM) deposition in the liver. It is typical of many chronic liver diseases, including cirrhosis, and effective drugs are needed. In this study, we explored the protective effect of bergenin on liver fibrosis induced by carbon tetrachloride and bile duct ligation. A variety of molecular biological methods (qRT-PCR, western blotting, and immunohistochemistry) were employed to confirm the increased degree of hepatocyte injury and ECM formation in the disease model, consistent with autophagy and activation of the TGF-<i>β</i> pathway. Bergenin activated PPAR-<i>γ</i> and inhibited TGF-<i>β</i> and autophagy and decreased liver fibrosis by inhibiting hepatocyte necrosis and ECM formation in a dose-dependent manner. The results suggest that bergenin may be a promising drug candidate for the treatment of liver fibrosis.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38854144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cholesteatoma is characterized by both the overgrowth of hyperkeratinized squamous epithelium and bone erosion. However, the exact mechanism underlying the hyperproliferative ability of cholesteatoma remains unknown. In this study, we investigated PPAR β/δ expression in human surgical specimens of cholesteatoma and analyzed its functional role as a regulator of epithelial keratinocyte hyperproliferation. We found that the expression of PPAR β/δ was significantly upregulated in cholesteatoma and ligand-activated PPAR β/δ markedly promoted the proliferation of cholesteatoma keratinocytes. Furthermore, we showed that PPAR β/δ activation increased PDK1 expression and decreased PTEN generation, which led to increased phosphorylation of AKT and GSK3β and increased the expression level of Cyclin D1. Overall, our data suggested that the proliferating effect of PPAR β/δ on the cholesteatoma keratinocytes was mediated by the positive regulation of the PDK1/PTEN/AKT/GSK3β/Cyclin D1 pathway. These findings warranted further investigation of PPAR β/δ as a therapeutic target for recurrent or residual cholesteatoma.
{"title":"Ligand-Activated Peroxisome Proliferator-Activated Receptor <i>β</i>/<i>δ</i> Facilitates Cell Proliferation in Human Cholesteatoma Keratinocytes.","authors":"Chen Zhang, Yang-Wenyi Liu, Zhangcai Chi, Bing Chen","doi":"10.1155/2020/8864813","DOIUrl":"https://doi.org/10.1155/2020/8864813","url":null,"abstract":"<p><p>Cholesteatoma is characterized by both the overgrowth of hyperkeratinized squamous epithelium and bone erosion. However, the exact mechanism underlying the hyperproliferative ability of cholesteatoma remains unknown. In this study, we investigated PPAR <i>β</i>/<i>δ</i> expression in human surgical specimens of cholesteatoma and analyzed its functional role as a regulator of epithelial keratinocyte hyperproliferation. We found that the expression of PPAR <i>β</i>/<i>δ</i> was significantly upregulated in cholesteatoma and ligand-activated PPAR <i>β</i>/<i>δ</i> markedly promoted the proliferation of cholesteatoma keratinocytes. Furthermore, we showed that PPAR <i>β</i>/<i>δ</i> activation increased PDK1 expression and decreased PTEN generation, which led to increased phosphorylation of AKT and GSK3<i>β</i> and increased the expression level of Cyclin D1. Overall, our data suggested that the proliferating effect of PPAR <i>β</i>/<i>δ</i> on the cholesteatoma keratinocytes was mediated by the positive regulation of the PDK1/PTEN/AKT/GSK3<i>β</i>/Cyclin D1 pathway. These findings warranted further investigation of PPAR <i>β</i>/<i>δ</i> as a therapeutic target for recurrent or residual cholesteatoma.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38804542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-22eCollection Date: 2020-01-01DOI: 10.1155/2020/6633022
Xianjin Du, Miao Wu, Dan Tian, Jianlin Zhou, Lu Wang, Liying Zhan
The severity of sepsis may be associated with excessive inflammation, thus leading to acute liver injury. MicroRNA-21 is highly expressed in the liver of a variety of inflammation-related diseases, and PPARα is also proved to participate in regulating inflammation. In the present study, the LPS-induced sepsis model was established. We found that microRNA-21 expression was upregulated in the liver of sepsis mice, and microRNA-21 inhibition significantly reduced the liver injury. The expression of liver injury markers, inflammation cytokines, and PPARα in the septic mice was higher than in antagomir-21 treated septic mice. In addition, we also found that PPARα is the target gene of microRNA-21; PPARα antagonist GW6471 could reverse the effect of antagomir-21. In conclusion, our study illustrated that microRNA-21 exacerbate acute liver injury in sepsis mice by inhibiting PPARα expression.
{"title":"MicroRNA-21 Contributes to Acute Liver Injury in LPS-Induced Sepsis Mice by Inhibiting PPAR<i>α</i> Expression.","authors":"Xianjin Du, Miao Wu, Dan Tian, Jianlin Zhou, Lu Wang, Liying Zhan","doi":"10.1155/2020/6633022","DOIUrl":"https://doi.org/10.1155/2020/6633022","url":null,"abstract":"<p><p>The severity of sepsis may be associated with excessive inflammation, thus leading to acute liver injury. MicroRNA-21 is highly expressed in the liver of a variety of inflammation-related diseases, and PPAR<i>α</i> is also proved to participate in regulating inflammation. In the present study, the LPS-induced sepsis model was established. We found that microRNA-21 expression was upregulated in the liver of sepsis mice, and microRNA-21 inhibition significantly reduced the liver injury. The expression of liver injury markers, inflammation cytokines, and PPAR<i>α</i> in the septic mice was higher than in antagomir-21 treated septic mice. In addition, we also found that PPAR<i>α</i> is the target gene of microRNA-21; PPAR<i>α</i> antagonist GW6471 could reverse the effect of antagomir-21. In conclusion, our study illustrated that microRNA-21 exacerbate acute liver injury in sepsis mice by inhibiting PPAR<i>α</i> expression.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38804541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-14eCollection Date: 2020-01-01DOI: 10.1155/2020/6661642
Wanshun Wen, Jinlin Wang, Biyu Zhang, Jun Wang
Inflammation caused by neuropathy contributes to the development of neuropathic pain (NP), but the exact mechanism still needs to be understood. Peroxisome proliferator-activated receptor α (PPARα), an important inflammation regulator, might participate in the inflammation in NP. To explore the role of PPARα in NP, the effects of PPARα agonist WY-14643 on chronic constriction injury (CCI) rats were evaluated. The results showed that WY-14643 stimulation could decrease inflammation and relieve neuropathic pain, which was relative with the activation of PPARα. In addition, we also found that the SIRT1/NF-κB pathway was involved in the WY-14643-induced anti-inflammation in NP, and activation of PPARα increased SIRT1 expression, thus reducing the proinflammatory function of NF-κB. These data suggested that WY-14643 might serve as an inflammation mediator, which may be a potential therapy option for NP.
{"title":"PPAR<i>α</i> Agonist WY-14643 Relieves Neuropathic Pain through SIRT1-Mediated Deacetylation of NF-<i>κ</i>B.","authors":"Wanshun Wen, Jinlin Wang, Biyu Zhang, Jun Wang","doi":"10.1155/2020/6661642","DOIUrl":"https://doi.org/10.1155/2020/6661642","url":null,"abstract":"<p><p>Inflammation caused by neuropathy contributes to the development of neuropathic pain (NP), but the exact mechanism still needs to be understood. Peroxisome proliferator-activated receptor <i>α</i> (PPAR<i>α</i>), an important inflammation regulator, might participate in the inflammation in NP. To explore the role of PPAR<i>α</i> in NP, the effects of PPAR<i>α</i> agonist WY-14643 on chronic constriction injury (CCI) rats were evaluated. The results showed that WY-14643 stimulation could decrease inflammation and relieve neuropathic pain, which was relative with the activation of PPAR<i>α</i>. In addition, we also found that the SIRT1/NF-<i>κ</i>B pathway was involved in the WY-14643-induced anti-inflammation in NP, and activation of PPAR<i>α</i> increased SIRT1 expression, thus reducing the proinflammatory function of NF-<i>κ</i>B. These data suggested that WY-14643 might serve as an inflammation mediator, which may be a potential therapy option for NP.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/6661642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38794143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-29eCollection Date: 2020-01-01DOI: 10.1155/2020/8859017
Olga I Rudko, Artemii V Tretiakov, Elena A Naumova, Eugene A Klimov
Peroxisome proliferator-activated receptor (PPAR) group includes three isoforms encoded by PPARG, PPARA, and PPARD genes. High concentrations of PPARs are found in parts of the brain linked to anxiety development, including hippocampus and amygdala. Among three PPAR isoforms, PPARG demonstrates the highest expression in CNS, where it can be found in neurons, astrocytes, and glial cells. Herein, the highest PPARG expression occurs in amygdala. However, little is known considering possible connections between PPARs and anxiety behavior. We reviewed possible connections between PPARs and anxiety. We used the Pathway Studio software (Elsevier). Signal pathways were created according to previously developed algorithms. SNEA was performed in Pathway Studio. Current study revealed 14 PPAR-regulated proteins linked to anxiety. Possible mechanism of PPAR involvement in neuroinflammation protection is proposed. Signal pathway reconstruction and reviewing aimed to reveal possible connection between PPARG and CCK-ergic system was conducted. Said analysis revealed that PPARG-dependent regulation of MME and ACE peptidase expression may affect levels of nonhydrolysed, i.e., active CCK-4. Impairments in PPARG regulation and following MME and ACE peptidase expression impairments in amygdala may be the possible mechanism leading to pathological anxiety development, with brain CCK-4 accumulation being a key link. Literature data analysis and signal pathway reconstruction and reviewing revealed two possible mechanisms of peroxisome proliferator-activated receptors involvement in pathological anxiety: (1) cytokine expression and neuroinflammation mechanism and (2) regulation of peptidases targeted to anxiety-associated neuropeptides, primarily CCK-4, mechanism.
{"title":"Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction.","authors":"Olga I Rudko, Artemii V Tretiakov, Elena A Naumova, Eugene A Klimov","doi":"10.1155/2020/8859017","DOIUrl":"https://doi.org/10.1155/2020/8859017","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor (PPAR) group includes three isoforms encoded by PPARG, PPARA, and PPARD genes. High concentrations of PPARs are found in parts of the brain linked to anxiety development, including hippocampus and amygdala. Among three PPAR isoforms, PPARG demonstrates the highest expression in CNS, where it can be found in neurons, astrocytes, and glial cells. Herein, the highest PPARG expression occurs in amygdala. However, little is known considering possible connections between PPARs and anxiety behavior. We reviewed possible connections between PPARs and anxiety. We used the Pathway Studio software (Elsevier). Signal pathways were created according to previously developed algorithms. SNEA was performed in Pathway Studio. Current study revealed 14 PPAR-regulated proteins linked to anxiety. Possible mechanism of PPAR involvement in neuroinflammation protection is proposed. Signal pathway reconstruction and reviewing aimed to reveal possible connection between PPARG and CCK-ergic system was conducted. Said analysis revealed that PPARG-dependent regulation of MME and ACE peptidase expression may affect levels of nonhydrolysed, i.e., active CCK-4. Impairments in PPARG regulation and following MME and ACE peptidase expression impairments in amygdala may be the possible mechanism leading to pathological anxiety development, with brain CCK-4 accumulation being a key link. Literature data analysis and signal pathway reconstruction and reviewing revealed two possible mechanisms of peroxisome proliferator-activated receptors involvement in pathological anxiety: (1) cytokine expression and neuroinflammation mechanism and (2) regulation of peptidases targeted to anxiety-associated neuropeptides, primarily CCK-4, mechanism.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8859017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38366716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-27eCollection Date: 2020-01-01DOI: 10.1155/2020/8894525
María Sánchez-Aguilar, Luz Ibarra-Lara, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Juan Carlos Torres-Narváez, Elizabeth Carreón-Torres, Alicia Sánchez-Mendoza, María Esther Rubio-Ruíz
The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups: (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.
{"title":"Nonclassical Axis of the Renin-Angiotensin System and Neprilysin: Key Mediators That Underlie the Cardioprotective Effect of PPAR-Alpha Activation during Myocardial Ischemia in a Metabolic Syndrome Model.","authors":"María Sánchez-Aguilar, Luz Ibarra-Lara, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Juan Carlos Torres-Narváez, Elizabeth Carreón-Torres, Alicia Sánchez-Mendoza, María Esther Rubio-Ruíz","doi":"10.1155/2020/8894525","DOIUrl":"https://doi.org/10.1155/2020/8894525","url":null,"abstract":"<p><p>The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups: (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8894525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38743986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-26eCollection Date: 2020-01-01DOI: 10.1155/2020/8889612
Hua Guo, Qinglan Zhang, Haipo Yuan, Lin Zhou, Fang-Fang Li, Sheng-Ming Wang, Gang Shi, Maojuan Wang
Inflammation accounts for the process of type II diabetes mellitus (T2DM), the specific mechanism of which is still to be elucidated yet. Nitric oxide (NO), a critical inflammation regulator, the role of which is the inflammation of T2DM, is rarely reported. Therefore, our study is aimed at exploring the effect of NO on the inflammation in T2DM and the corresponding mechanism. We analyzed the NO levels in plasma samples from T2DM patients and paired healthy adults by Nitric Oxide Analyzer then measured the expression of inflammatory cytokines (C-reactive protein, heptoglobin, IL-1β, TNF-α, IL-6) in insulin-induced HepG2 cells treated with NO donor or NO scavenger, and the PPARγ, eNOS, C-reactive protein, heptoglobin, IL-1β, TNF-α, and IL-6 levels were detected by RT-PCR and western blot in insulin-induced HepG2 cells transfected with si-PPARγ. The results showed that excess NO increased the inflammation marker levels in T2DM, which is activated by the PPARγ/eNOS pathway. These findings will strengthen the understanding of NO in T2DM and provide a new target for the treatment of T2DM.
{"title":"Nitric Oxide Mediates Inflammation in Type II Diabetes Mellitus through the PPAR<i>γ</i>/eNOS Signaling Pathway.","authors":"Hua Guo, Qinglan Zhang, Haipo Yuan, Lin Zhou, Fang-Fang Li, Sheng-Ming Wang, Gang Shi, Maojuan Wang","doi":"10.1155/2020/8889612","DOIUrl":"https://doi.org/10.1155/2020/8889612","url":null,"abstract":"<p><p>Inflammation accounts for the process of type II diabetes mellitus (T2DM), the specific mechanism of which is still to be elucidated yet. Nitric oxide (NO), a critical inflammation regulator, the role of which is the inflammation of T2DM, is rarely reported. Therefore, our study is aimed at exploring the effect of NO on the inflammation in T2DM and the corresponding mechanism. We analyzed the NO levels in plasma samples from T2DM patients and paired healthy adults by Nitric Oxide Analyzer then measured the expression of inflammatory cytokines (C-reactive protein, heptoglobin, IL-1<i>β</i>, TNF-<i>α</i>, IL-6) in insulin-induced HepG2 cells treated with NO donor or NO scavenger, and the PPAR<i>γ</i>, eNOS, C-reactive protein, heptoglobin, IL-1<i>β</i>, TNF-<i>α</i>, and IL-6 levels were detected by RT-PCR and western blot in insulin-induced HepG2 cells transfected with si-PPAR<i>γ</i>. The results showed that excess NO increased the inflammation marker levels in T2DM, which is activated by the PPAR<i>γ</i>/eNOS pathway. These findings will strengthen the understanding of NO in T2DM and provide a new target for the treatment of T2DM.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8889612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38352121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-10-09eCollection Date: 2020-01-01DOI: 10.1155/2020/6529057
Vladimir Sobolev, Anastasia Nesterova, Anna Soboleva, Evgenia Dvoriankova, Anastas Piruzyan, Dzerassa Mildzikhova, Irina Korsunskaya, Oxana Svitich
Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.
{"title":"The Model of <i>PPARγ</i>-Downregulated Signaling in Psoriasis.","authors":"Vladimir Sobolev, Anastasia Nesterova, Anna Soboleva, Evgenia Dvoriankova, Anastas Piruzyan, Dzerassa Mildzikhova, Irina Korsunskaya, Oxana Svitich","doi":"10.1155/2020/6529057","DOIUrl":"https://doi.org/10.1155/2020/6529057","url":null,"abstract":"<p><p>Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (<i>PPARγ</i>) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of <i>PPARγ</i> expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of <i>PPARγ</i>-downregulated signaling in psoriasis. We hypothesize that the expression of <i>IL17</i>, <i>STAT3</i>, <i>FOXP3</i>, and <i>RORC</i> and <i>FOSL1</i> genes in psoriatic skin is correlated with the level of <i>PPARγ</i> expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/6529057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38657491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peroxisome proliferator-activated receptors (PPARs) are members of nuclear transcription factors. The functions of the PPAR family (PPARA, PPARD, and PPARG) and their coactivators (PPARGC1A and PPARGC1B) in maintenance of lipid and glucose homeostasis have been unveiled. However, the roles of PPARs in cancer development remain elusive. In this work, we made use of 11,057 samples across 33 TCGA tumor types to analyze the relationship between PPAR transcriptional expression and tumorigenesis as well as drug sensitivity. We performed multidimensional analyses on PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B, including differential expression analysis in pan-cancer, immune subtype analysis, clinical analysis, tumor purity analysis, stemness correlation analysis, and drug responses. PPARs and their coactivators expressed differently in different types of cancers, in different immune subtypes. This analysis reveals various expression patterns of the PPAR family at a level of pan-cancer and provides new clues for the therapeutic strategies of cancer.
{"title":"The Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Pan-Cancer.","authors":"Runzhi Huang, Jiaqi Zhang, Mingxiao Li, Penghui Yan, Huabin Yin, Suna Zhai, Xiaolong Zhu, Peng Hu, Jiaxin Zhang, Ling Huang, Man Li, Zehui Sun, Tong Meng, Daoke Yang, Zongqiang Huang","doi":"10.1155/2020/6527564","DOIUrl":"https://doi.org/10.1155/2020/6527564","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptors (PPARs) are members of nuclear transcription factors. The functions of the PPAR family (PPARA, PPARD, and PPARG) and their coactivators (PPARGC1A and PPARGC1B) in maintenance of lipid and glucose homeostasis have been unveiled. However, the roles of PPARs in cancer development remain elusive. In this work, we made use of 11,057 samples across 33 TCGA tumor types to analyze the relationship between PPAR transcriptional expression and tumorigenesis as well as drug sensitivity. We performed multidimensional analyses on PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B, including differential expression analysis in pan-cancer, immune subtype analysis, clinical analysis, tumor purity analysis, stemness correlation analysis, and drug responses. PPARs and their coactivators expressed differently in different types of cancers, in different immune subtypes. This analysis reveals various expression patterns of the PPAR family at a level of pan-cancer and provides new clues for the therapeutic strategies of cancer.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/6527564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38466194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study is aimed at using genes related to the peroxisome proliferator-activated receptor (PPAR) pathway to establish a prognostic risk model in kidney renal clear cell carcinoma (KIRC).
Methods: For this study, we first found the PPAR pathway-related genes on the gene set enrichment analysis (GSEA) website and found the KIRC mRNA expression data and clinical data through TCGA database. Subsequently, we used R language and multiple R language expansion packages to analyze the expression, hazard ratio analysis, and coexpression analysis of PPAR pathway-related genes in KIRC. Afterward, using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website, we established the protein-protein interaction (PPI) network of genes related to the PPAR pathway. After that, we used LASSO regression curve analysis to establish a prognostic survival model in KIRC. Finally, based on the model, we conducted correlation analysis of the clinicopathological characteristics, univariate analysis, and multivariate analysis.
Results: We found that most of the genes related to the PPAR pathway had different degrees of expression differences in KIRC. Among them, the high expression of 27 genes is related to low survival rate of KIRC patients, and the high expression of 13 other genes is related to their high survival rate. Most importantly, we used 13 of these genes successfully to establish a risk model that could accurately predict patients' prognosis. There is a clear correlation between this model and metastasis, tumor, stage, grade, and fustat.
Conclusions: To the best of our knowledge, this is the first study to analyze the entire PPAR pathway in KIRC in detail and successfully establish a risk model for patient prognosis. We believe that our research can provide valuable data for future researchers and clinicians.
研究目的本研究旨在利用过氧化物酶体增殖激活受体(PPAR)通路相关基因建立肾透明细胞癌(KIRC)的预后风险模型:在这项研究中,我们首先在基因组富集分析(GSEA)网站上找到了 PPAR 通路相关基因,并通过 TCGA 数据库找到了 KIRC mRNA 表达数据和临床数据。随后,我们使用 R 语言和多个 R 语言扩展包分析了 PPAR 通路相关基因在 KIRC 中的表达、危险比分析和共表达分析。随后,我们利用STRING(Search Tool for the Retrieval of Interacting Genes/Proteins)网站,建立了PPAR通路相关基因的蛋白-蛋白相互作用(PPI)网络。之后,我们利用 LASSO 回归曲线分析法建立了 KIRC 的预后生存模型。最后,基于该模型,我们对临床病理特征进行了相关性分析、单变量分析和多变量分析:结果:我们发现大多数与 PPAR 通路相关的基因在 KIRC 中都有不同程度的表达差异。其中,27 个基因的高表达与 KIRC 患者的低存活率有关,另外 13 个基因的高表达与患者的高存活率有关。最重要的是,我们成功地利用其中 13 个基因建立了一个风险模型,该模型可以准确预测患者的预后。该模型与转移、肿瘤、分期、分级和 fustat 有明显的相关性:据我们所知,这是第一项详细分析 KIRC 中整个 PPAR 通路并成功建立患者预后风险模型的研究。我们相信,我们的研究能为未来的研究人员和临床医生提供有价值的数据。
{"title":"A New Prognostic Risk Model Based on PPAR Pathway-Related Genes in Kidney Renal Clear Cell Carcinoma.","authors":"Yingkun Xu, Xiunan Li, Yuqing Han, Zilong Wang, Chenglin Han, Ningke Ruan, Jianyi Li, Xiao Yu, Qinghua Xia, Guangzhen Wu","doi":"10.1155/2020/6937475","DOIUrl":"10.1155/2020/6937475","url":null,"abstract":"<p><strong>Objective: </strong>This study is aimed at using genes related to the peroxisome proliferator-activated receptor (PPAR) pathway to establish a prognostic risk model in kidney renal clear cell carcinoma (KIRC).</p><p><strong>Methods: </strong>For this study, we first found the PPAR pathway-related genes on the gene set enrichment analysis (GSEA) website and found the KIRC mRNA expression data and clinical data through TCGA database. Subsequently, we used R language and multiple R language expansion packages to analyze the expression, hazard ratio analysis, and coexpression analysis of PPAR pathway-related genes in KIRC. Afterward, using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) website, we established the protein-protein interaction (PPI) network of genes related to the PPAR pathway. After that, we used LASSO regression curve analysis to establish a prognostic survival model in KIRC. Finally, based on the model, we conducted correlation analysis of the clinicopathological characteristics, univariate analysis, and multivariate analysis.</p><p><strong>Results: </strong>We found that most of the genes related to the PPAR pathway had different degrees of expression differences in KIRC. Among them, the high expression of 27 genes is related to low survival rate of KIRC patients, and the high expression of 13 other genes is related to their high survival rate. Most importantly, we used 13 of these genes successfully to establish a risk model that could accurately predict patients' prognosis. There is a clear correlation between this model and metastasis, tumor, stage, grade, and fustat.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to analyze the entire PPAR pathway in KIRC in detail and successfully establish a risk model for patient prognosis. We believe that our research can provide valuable data for future researchers and clinicians.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2020-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38466195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}