Samya Mere L. Rodrigues, Carolina F. Ximenes, Nathália Rodrigues, Karoline Ronconi, Anna Karolina Nascimento Costa, Livia Barroca Vieira, Maria Luiza Yago da Silva, Katyana K. S. Ferreira, Marcos Eliezeck, Sergio Scalzo, André Monteiro, Bruno Sanches, Thiago Spalenza, Aurélia Araújo Fernandes, Silvia Guatimosim, Kurt J. Varner, Eduardo Hertel Ribeiro, Ivanita Stefanon
Aim
Young women exhibit lower rates of cardiovascular disease (CVD) than age-matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post-menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen-deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility.
Methods
Wistar rats were divided into four groups: Sham, Ovariectomy-induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days.
Results
Both apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates.
Conclusion
We concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency.
{"title":"Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX-4 in female hormone deprivation rats","authors":"Samya Mere L. Rodrigues, Carolina F. Ximenes, Nathália Rodrigues, Karoline Ronconi, Anna Karolina Nascimento Costa, Livia Barroca Vieira, Maria Luiza Yago da Silva, Katyana K. S. Ferreira, Marcos Eliezeck, Sergio Scalzo, André Monteiro, Bruno Sanches, Thiago Spalenza, Aurélia Araújo Fernandes, Silvia Guatimosim, Kurt J. Varner, Eduardo Hertel Ribeiro, Ivanita Stefanon","doi":"10.1111/apha.70007","DOIUrl":"10.1111/apha.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Young women exhibit lower rates of cardiovascular disease (CVD) than age-matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post-menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen-deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wistar rats were divided into four groups: Sham, Ovariectomy-induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emil Rindom, Katja Bundgaard Last, Anja Svane, Asger Fammé, Per G. Henriksen, Jean Farup, Niels Jessen, Frank Vincenzo de Paoli, Tobias Wang
Aim
Snakes exhibit remarkable physiological shifts when their large meals induce robust postprandial growth after prolonged fasting. To understand the regulatory mechanisms underlying this rapid metabolic transition, we examined the regulation of protein synthesis in pythons, focusing on processes driving early postprandial tissue remodeling and growth.
Methods
Using the SUnSET method with puromycin labeling, we measured in vivo protein synthesis in fasting and digesting snakes at multiple post-feeding intervals. Pyloric ligation, pancreatectomy, and plasma transfusions were performed to explore the roles of gastrointestinal luminal signaling and pancreatic function across key tissues.
Results
We observed profound and early stimulation of protein synthesis in gastrointestinal tissues and skeletal muscle already 3 h after ingestion, before any measurable rise in plasma amino acids from the meal. The gastrointestinal stimulation appears to be driven by luminal factors, while the stimulation of skeletal muscle protein synthesis is humoral with pancreatic insulin release as an integral mediator. The pre-absorptive anabolic activity is supported by the release of amino acids from the breakdown of endogenous proteins.
Conclusions
Our findings suggest that snakes initiate protein synthesis via distinct, tissue-specific pathways preceding nutrient absorption. This “pay before pumping” model shows how early protein synthesis prepares the digestive and muscular systems for later nutrient assimilation and growth. This intricate humoral regulation, involving a gut-pancreas-muscle axis, governs postprandial protein synthesis in snakes and provides insights into fundamental mechanisms driving metabolic adaptations and broader hyperplastic and hypertrophic responses.
{"title":"Rapid stimulation of protein synthesis in digesting snakes: Unveiling a novel gut-pancreas-muscle axis","authors":"Emil Rindom, Katja Bundgaard Last, Anja Svane, Asger Fammé, Per G. Henriksen, Jean Farup, Niels Jessen, Frank Vincenzo de Paoli, Tobias Wang","doi":"10.1111/apha.70006","DOIUrl":"10.1111/apha.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Snakes exhibit remarkable physiological shifts when their large meals induce robust postprandial growth after prolonged fasting. To understand the regulatory mechanisms underlying this rapid metabolic transition, we examined the regulation of protein synthesis in pythons, focusing on processes driving early postprandial tissue remodeling and growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the SUnSET method with puromycin labeling, we measured in vivo protein synthesis in fasting and digesting snakes at multiple post-feeding intervals. Pyloric ligation, pancreatectomy, and plasma transfusions were performed to explore the roles of gastrointestinal luminal signaling and pancreatic function across key tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed profound and early stimulation of protein synthesis in gastrointestinal tissues and skeletal muscle already 3 h after ingestion, before any measurable rise in plasma amino acids from the meal. The gastrointestinal stimulation appears to be driven by luminal factors, while the stimulation of skeletal muscle protein synthesis is humoral with pancreatic insulin release as an integral mediator. The pre-absorptive anabolic activity is supported by the release of amino acids from the breakdown of endogenous proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that snakes initiate protein synthesis via distinct, tissue-specific pathways preceding nutrient absorption. This “pay before pumping” model shows how early protein synthesis prepares the digestive and muscular systems for later nutrient assimilation and growth. This intricate humoral regulation, involving a gut-pancreas-muscle axis, governs postprandial protein synthesis in snakes and provides insights into fundamental mechanisms driving metabolic adaptations and broader hyperplastic and hypertrophic responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past two decades, it has become clear that against earlier assumptions, the respiratory tract is regularly populated by a variety of microbiota even down to the lowest parts of the lungs. New methods and technologies revealed distinct microbiome compositions and developmental trajectories in the differing parts of the respiratory tract of neonates and infants. In this review, we describe the current understanding of respiratory microbiota development in human neonates and highlight multiple factors that have been identified to impact human respiratory microbiome development including gestational age, mode of delivery, diet, antibiotic treatment, and early infections. Moreover, we discuss to date revealed respiratory microbiome–disease associations in infants and children that may indicate a potentially imprinting cross talk between microbial communities and the host immune system in the respiratory tract. It becomes obvious how insufficient our knowledge still is regarding the exact mechanisms underlying such cross talk in humans. Lastly, we highlight strong findings that emphasize the important role of the gut–lung axis in educating and driving pulmonary immunity. Further research is needed to better understand the host – respiratory microbiome interaction in order to enable the translation into microbiome-based strategies to protect and improve human respiratory health from early childhood.
{"title":"The neonate respiratory microbiome","authors":"Sabine Pirr, Maike Willers, Dorothee Viemann","doi":"10.1111/apha.14266","DOIUrl":"10.1111/apha.14266","url":null,"abstract":"<p>Over the past two decades, it has become clear that against earlier assumptions, the respiratory tract is regularly populated by a variety of microbiota even down to the lowest parts of the lungs. New methods and technologies revealed distinct microbiome compositions and developmental trajectories in the differing parts of the respiratory tract of neonates and infants. In this review, we describe the current understanding of respiratory microbiota development in human neonates and highlight multiple factors that have been identified to impact human respiratory microbiome development including gestational age, mode of delivery, diet, antibiotic treatment, and early infections. Moreover, we discuss to date revealed respiratory microbiome–disease associations in infants and children that may indicate a potentially imprinting cross talk between microbial communities and the host immune system in the respiratory tract. It becomes obvious how insufficient our knowledge still is regarding the exact mechanisms underlying such cross talk in humans. Lastly, we highlight strong findings that emphasize the important role of the gut–lung axis in educating and driving pulmonary immunity. Further research is needed to better understand the host – respiratory microbiome interaction in order to enable the translation into microbiome-based strategies to protect and improve human respiratory health from early childhood.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>In the context of cardiovascular health, potassium has long been the forgotten cation, overshadowed by sodium occupying the “superior” position in the alkali metal series, Group 1 of the periodic table of elements. Epidemiological and interventional clinical trials are beginning to shift the dial, revealing health benefits of diets rich in potassium. The physiological mechanisms are not fully resolved. In this issue of <i>Acta Physiologica</i> a study by Vitzhum and colleagues shows that increasing dietary potassium intake in mice reduces the sensitivity of the distal nephron to the sodium-retaining hormone aldosterone. Intriguingly, the accompanying anion may be the critical factor.<span><sup>1</sup></span></p><p>The adverse health impact of high salt (NaCl) intake has long been recognized and dominates discourse related to modern dietary practice.<span><sup>2</sup></span> Many countries have public health policies with aspirations to reduce salt intake. Dietary potassium does not garner the same attention, despite estimates that daily intake is habitually below the ~100 mmoles/day threshold of adequacy.<span><sup>3</sup></span> Indeed, when potassium is mentioned at all, it is common to caution against dietary overload and the risk of hyperkalemia in people with kidney disease, or those taking mineralocorticoid receptor (MR) antagonists and renin-angiotensin system blockers.<span><sup>4</sup></span></p><p>The story is changing. Observational evidence associates higher potassium with reduced cardiovascular events, reduced mortality and lower albuminuria.<span><sup>5-7</sup></span> Recent interventional studies show that substitution of regular table salt (100% NaCl) with “low-salt” (75% NaCl and 25% KCl) lowers blood pressure and reduces cardiovascular events; benefits that seem to reflect an increase in potassium intake rather than the reduction in salt intake.<span><sup>8, 9</sup></span> Indeed, a meta-analysis of randomized controlled trials finds that oral potassium supplements reduces systolic blood pressure by ~3 mmHg, an effect size similar to that of monotherapy with front-line antihypertensive drugs.<span><sup>10</sup></span> The physiological mechanisms underpinning such benefits are not well understood. One possibility is that a potassium-rich diet facilitates sodium excretion by the kidneys. Indeed, the diuretic properties of oral potassium salts have long been recognized and the effect of potassium intake on kidney sodium transporter function has been a subject of intense research in the last decade. For example, NCC is the sodium chloride cotransporter in the apical membrane of the distal convoluted tubule and the target of thiazide diuretics.<span><sup>11</sup></span> It is now widely accepted that provision of oral potassium deactivates NCC.<span><sup>11, 12</sup></span> The intracellular mechanism is delineated: elevated extracellular potassium increases intracellular chloride concentration, directly inhibiting the kinase WNK
{"title":"Potassium intake to regulate sodium excretion? Don't forget the anion","authors":"Matthew A. Bailey","doi":"10.1111/apha.14260","DOIUrl":"10.1111/apha.14260","url":null,"abstract":"<p>In the context of cardiovascular health, potassium has long been the forgotten cation, overshadowed by sodium occupying the “superior” position in the alkali metal series, Group 1 of the periodic table of elements. Epidemiological and interventional clinical trials are beginning to shift the dial, revealing health benefits of diets rich in potassium. The physiological mechanisms are not fully resolved. In this issue of <i>Acta Physiologica</i> a study by Vitzhum and colleagues shows that increasing dietary potassium intake in mice reduces the sensitivity of the distal nephron to the sodium-retaining hormone aldosterone. Intriguingly, the accompanying anion may be the critical factor.<span><sup>1</sup></span></p><p>The adverse health impact of high salt (NaCl) intake has long been recognized and dominates discourse related to modern dietary practice.<span><sup>2</sup></span> Many countries have public health policies with aspirations to reduce salt intake. Dietary potassium does not garner the same attention, despite estimates that daily intake is habitually below the ~100 mmoles/day threshold of adequacy.<span><sup>3</sup></span> Indeed, when potassium is mentioned at all, it is common to caution against dietary overload and the risk of hyperkalemia in people with kidney disease, or those taking mineralocorticoid receptor (MR) antagonists and renin-angiotensin system blockers.<span><sup>4</sup></span></p><p>The story is changing. Observational evidence associates higher potassium with reduced cardiovascular events, reduced mortality and lower albuminuria.<span><sup>5-7</sup></span> Recent interventional studies show that substitution of regular table salt (100% NaCl) with “low-salt” (75% NaCl and 25% KCl) lowers blood pressure and reduces cardiovascular events; benefits that seem to reflect an increase in potassium intake rather than the reduction in salt intake.<span><sup>8, 9</sup></span> Indeed, a meta-analysis of randomized controlled trials finds that oral potassium supplements reduces systolic blood pressure by ~3 mmHg, an effect size similar to that of monotherapy with front-line antihypertensive drugs.<span><sup>10</sup></span> The physiological mechanisms underpinning such benefits are not well understood. One possibility is that a potassium-rich diet facilitates sodium excretion by the kidneys. Indeed, the diuretic properties of oral potassium salts have long been recognized and the effect of potassium intake on kidney sodium transporter function has been a subject of intense research in the last decade. For example, NCC is the sodium chloride cotransporter in the apical membrane of the distal convoluted tubule and the target of thiazide diuretics.<span><sup>11</sup></span> It is now widely accepted that provision of oral potassium deactivates NCC.<span><sup>11, 12</sup></span> The intracellular mechanism is delineated: elevated extracellular potassium increases intracellular chloride concentration, directly inhibiting the kinase WNK","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allan Langlois, Julien Cherfan, Emmanuelle Meugnier, Ahmad Rida, Caroline Arous, Claude Peronet, Harzo Hamdard, Bader Zarrouki, Bernhard Wehrle-Haller, Michel Pinget, Siobhan M. Craige, Karim Bouzakri
Aim
Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored.
Methods
The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix).
Results
DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism.
Conclusion
Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.
{"title":"DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes","authors":"Allan Langlois, Julien Cherfan, Emmanuelle Meugnier, Ahmad Rida, Caroline Arous, Claude Peronet, Harzo Hamdard, Bader Zarrouki, Bernhard Wehrle-Haller, Michel Pinget, Siobhan M. Craige, Karim Bouzakri","doi":"10.1111/apha.14267","DOIUrl":"10.1111/apha.14267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miriam Di Mattia, Michele Sallese, Loris Riccardo Lopetuso
Different physiological and pathological situations can produce alterations in the cell's endoplasmic reticulum (ER), leading to a condition known as ER stress, which can trigger an intricate intracellular signal transduction system known as the unfolded protein response (UPR). UPR is primarily tailored to restore proteostasis and ER equilibrium; otherwise, if ER stress persists, it can cause programmed cell death as a cytoprotective mechanism and drive inflammatory processes. Therefore, since intestinal cells strongly rely on UPR for their biological functions and unbalanced UPR has been linked to inflammatory, metabolic, and immune disorders, here we discussed the role of the UPR within the intestinal tract, focusing on the UPR contribution to inflammatory bowel disease development. Importantly, we also highlighted the promising potential of UPR components as therapeutic targets for intestinal inflammatory diseases.
{"title":"Unfolded protein response: An essential element of intestinal homeostasis and a potential therapeutic target for inflammatory bowel disease","authors":"Miriam Di Mattia, Michele Sallese, Loris Riccardo Lopetuso","doi":"10.1111/apha.14284","DOIUrl":"10.1111/apha.14284","url":null,"abstract":"<p>Different physiological and pathological situations can produce alterations in the cell's endoplasmic reticulum (ER), leading to a condition known as ER stress, which can trigger an intricate intracellular signal transduction system known as the unfolded protein response (UPR). UPR is primarily tailored to restore proteostasis and ER equilibrium; otherwise, if ER stress persists, it can cause programmed cell death as a cytoprotective mechanism and drive inflammatory processes. Therefore, since intestinal cells strongly rely on UPR for their biological functions and unbalanced UPR has been linked to inflammatory, metabolic, and immune disorders, here we discussed the role of the UPR within the intestinal tract, focusing on the UPR contribution to inflammatory bowel disease development. Importantly, we also highlighted the promising potential of UPR components as therapeutic targets for intestinal inflammatory diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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