Pub Date : 2024-05-02DOI: 10.1152/ajprenal.00062.2024
Katherine Pfister, Victoria Young, Brendon Frankel, Anne Silva Barbosa, Jordan Burton, Joanna Bons, Bob Zhang, Takuto Chiba, Rebecca Uhlean, Eric Goetzman, Birgit Schilling, Sunder Sims-Lucas
Acute Kidney Injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate ischemic AKI therapeutically, we need a better understanding of the physiological and cellular mechanisms underlying damage. Instances of ischemia are most damaging in Proximal Tubule Epithelial Cells (PTECs) where hypoxic signaling cascades, and perhaps more rapidly, posttranslational modifications (PTMs), act in concert to change cellular metabolism. Here we focus on the effects of the understudied PTM, lysine succinylation. We have previously shown a protective effect of protein hypersuccinylation on PTECs after depletion of the desuccinylase Sirtuin 5. General trends in the results suggested that hypersuccinylation led to upregulation of peroxisomal activity and was protective against kidney injury. Included in the list of changes was the Parkinson's-related deglycase Park7. There is little known about any links between peroxisome activity and Park7. In this study we show in vitro and in vivo that Park7 has a crucial role in protection from AKI, and upregulated peroxisome activity. These data in combination with published results of Park7's protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that succinylation of Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. This novel mechanism provides a potential therapeutic mechanism that can be targeted.
急性肾损伤（AKI）在住院病人中极为普遍，是导致慢性肾病和死亡率上升的重要风险因素。休克、创伤和移植导致的缺血是造成急性肾损伤的常见原因。为了从治疗上减轻缺血性 AKI，我们需要更好地了解损伤的生理和细胞机制。缺血对近端肾小管上皮细胞（PTECs）的损害最大，缺氧信号级联和翻译后修饰（PTMs）可能会更快地协同改变细胞的新陈代谢。在这里，我们重点研究了未被充分研究的 PTM--赖氨酸琥珀酰化的影响。我们之前已经证明，在去琥珀酰化酶 Sirtuin 5 失活后，蛋白质过度琥珀酰化对 PTEC 有保护作用。研究结果的总体趋势表明，过度琥珀酰化导致过氧物酶体活性上调，对肾损伤具有保护作用。与帕金森氏症相关的脱琥珀酰酶 Park7 也出现了变化。人们对过氧化物酶体活性与 Park7 之间的联系知之甚少。在这项研究中，我们在体外和体内发现，Park7 在保护肾脏免受 AKI 损伤和上调过氧化物酶体活性方面起着至关重要的作用。这些数据与已发表的有关 Park7 在心血管损伤和慢性肾病中的保护作用的研究结果相结合，使我们推测，Park7 的琥珀酰化可能会改善 AKI 导致的氧化损伤并防止疾病进展。这种新的机制提供了一种潜在的治疗机制，可以有的放矢。
{"title":"Succinylation of Park 7 Activates a Protective Metabolic Response to Acute Kidney Injury","authors":"Katherine Pfister, Victoria Young, Brendon Frankel, Anne Silva Barbosa, Jordan Burton, Joanna Bons, Bob Zhang, Takuto Chiba, Rebecca Uhlean, Eric Goetzman, Birgit Schilling, Sunder Sims-Lucas","doi":"10.1152/ajprenal.00062.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00062.2024","url":null,"abstract":"Acute Kidney Injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate ischemic AKI therapeutically, we need a better understanding of the physiological and cellular mechanisms underlying damage. Instances of ischemia are most damaging in Proximal Tubule Epithelial Cells (PTECs) where hypoxic signaling cascades, and perhaps more rapidly, posttranslational modifications (PTMs), act in concert to change cellular metabolism. Here we focus on the effects of the understudied PTM, lysine succinylation. We have previously shown a protective effect of protein hypersuccinylation on PTECs after depletion of the desuccinylase Sirtuin 5. General trends in the results suggested that hypersuccinylation led to upregulation of peroxisomal activity and was protective against kidney injury. Included in the list of changes was the Parkinson's-related deglycase Park7. There is little known about any links between peroxisome activity and Park7. In this study we show <i>in vitro</i> and <i>in vivo</i> that Park7 has a crucial role in protection from AKI, and upregulated peroxisome activity. These data in combination with published results of Park7's protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that succinylation of Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. This novel mechanism provides a potential therapeutic mechanism that can be targeted.","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1152/ajprenal.00126.2024
Alexander Staruschenko
American Journal of Physiology-Renal Physiology, Ahead of Print.
美国生理学杂志-肾脏生理学》，提前出版。
{"title":"SGLT2 inhibitors: not every drug has the same effect","authors":"Alexander Staruschenko","doi":"10.1152/ajprenal.00126.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00126.2024","url":null,"abstract":"American Journal of Physiology-Renal Physiology, Ahead of Print. <br/>","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00274.2023
Dana Bielopolski, Luca Musante, Ewout J. Hoorn, Henrik Molina, Douglas Barrows, Thomas Carroll, Michael A. Harding, Samantha Upson, Adam Qureshi, Max M. Weder, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger
American Journal of Physiology-Renal Physiology, Ahead of Print.
美国生理学杂志-肾脏生理学》，提前出版。
{"title":"Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles","authors":"Dana Bielopolski, Luca Musante, Ewout J. Hoorn, Henrik Molina, Douglas Barrows, Thomas Carroll, Michael A. Harding, Samantha Upson, Adam Qureshi, Max M. Weder, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger","doi":"10.1152/ajprenal.00274.2023","DOIUrl":"https://doi.org/10.1152/ajprenal.00274.2023","url":null,"abstract":"American Journal of Physiology-Renal Physiology, Ahead of Print. <br/>","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00376.2023
Kyungho Lee, Sepideh Gharaie, Johanna T. Kurzhagen, Andrea M. Newman-Rivera, Lois J. Arend, Sanjeev Noel, Hamid Rabb
T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR+ CD4- CD8-), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental AKI. However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared to gold-standard anti-inflammatory CD4+ Tregs. In vitro effects of DN T cells and Tregs on renal tubular epithelial cell (RTEC) repair after injury were quantified with live-cell analysis. DN T cells, Tregs, CD4 or vehicle were adoptively transferred after severe AKI. Glomerular filtration rate (GFR) was measured using FITC-sinistrin. Fibrosis was assessed with Masson's trichrome staining. Profibrotic genes were measured with qRT-PCR. Percentages and the numbers of DN T cells substantially decreased during repair phase after severe AKI, as well as their activation and proliferation. Both DN T cells and Tregs accelerated RTEC cell repair in vitro. Post-AKI transfer of DN T cells reduced kidney fibrosis and improved GFR, as did Treg transfer. DN T cell transfer lowered TGFβ1 and αSMA expression. DN T cells reduced effector-memory CD4+ T cells and IL-17 expression. DN T cells undergo quantitative and phenotypical changes after severe AKI, accelerate RTEC repair in vitro as well as improve GFR and renal fibrosis in vivo. DN T cells have potential as immunotherapy to accelerate repair after AKI.
T 细胞介导器官损伤和修复。以前曾证实，一部分被称为双阴性（DN）T 细胞（TCR+ CD4- CD8-）的非常规肾脏 T 细胞具有抗炎特性，能保护中度实验性 AKI 免受早期损伤。然而，它们在 AKI 后修复中的作用尚未得到研究。我们假设 DN T 细胞介导重度 AKI 后的修复。C57B6 小鼠接受了严重的（40 分钟）单侧缺血再灌注损伤（IRI）。通过流式细胞术研究了肾脏 DN T 细胞，并与黄金标准抗炎 CD4+ Tregs 进行了比较。通过活细胞分析量化了DN T细胞和Tregs对损伤后肾小管上皮细胞（RTEC）修复的体外效应。在重度AKI后采用DN T细胞、Tregs、CD4或载体进行移植。肾小球滤过率（GFR）用FITC-sinistrin测定。纤维化用马森氏三色染色法进行评估。用 qRT-PCR 测定坏死基因。在严重 AKI 后的修复阶段，DN T 细胞的百分比和数量大幅下降，其活化和增殖也大幅减少。DN T细胞和Tregs都能加速RTEC细胞的体外修复。AKI 后转入 DN T 细胞与转入 Treg 一样，都能减少肾脏纤维化并改善肾小球滤过率。DN T细胞转移降低了TGFβ1和αSMA的表达。DN T 细胞减少了效应记忆 CD4+ T 细胞和 IL-17 的表达。DN T细胞在严重AKI后会发生量变和表型变化，在体外加速RTEC修复，在体内改善GFR和肾脏纤维化。DN T细胞具有作为免疫疗法加速AKI后修复的潜力。
{"title":"Double-negative T cells have a reparative role after experimental severe ischemic acute kidney injury","authors":"Kyungho Lee, Sepideh Gharaie, Johanna T. Kurzhagen, Andrea M. Newman-Rivera, Lois J. Arend, Sanjeev Noel, Hamid Rabb","doi":"10.1152/ajprenal.00376.2023","DOIUrl":"https://doi.org/10.1152/ajprenal.00376.2023","url":null,"abstract":"T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR<sup>+</sup> CD4<sup>-</sup> CD8<sup>-</sup>), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental AKI. However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared to gold-standard anti-inflammatory CD4<sup>+</sup> Tregs. In vitro effects of DN T cells and Tregs on renal tubular epithelial cell (RTEC) repair after injury were quantified with live-cell analysis. DN T cells, Tregs, CD4 or vehicle were adoptively transferred after severe AKI. Glomerular filtration rate (GFR) was measured using FITC-sinistrin. Fibrosis was assessed with Masson's trichrome staining. Profibrotic genes were measured with qRT-PCR. Percentages and the numbers of DN T cells substantially decreased during repair phase after severe AKI, as well as their activation and proliferation. Both DN T cells and Tregs accelerated RTEC cell repair in vitro. Post-AKI transfer of DN T cells reduced kidney fibrosis and improved GFR, as did Treg transfer. DN T cell transfer lowered TGFβ1 and αSMA expression. DN T cells reduced effector-memory CD4<sup>+</sup> T cells and IL-17 expression. DN T cells undergo quantitative and phenotypical changes after severe AKI, accelerate RTEC repair in vitro as well as improve GFR and renal fibrosis in vivo. DN T cells have potential as immunotherapy to accelerate repair after AKI.","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00051.2024
Brittni N. Moore, Alexandra D. Medcalf, Rachel Q. Muir, Chudan Xu, Francine Z. Marques, Jennifer L. Pluznick
The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We employed enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-free mice), plasma aldosterone is significantly increased compared to conventional animals (in both females and males), but PRA is not. Understanding how gut microbiota influence aldosterone levels could provide valuable insights into the development and treatment of hypertension and/or primary aldosteronism. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications to help regulate blood pressure via microbiota-based changes to aldosterone.
肠道微生物群调节许多与心血管健康和疾病相关的重要宿主生理过程；然而，肠道微生物群对醛固酮的影响尚不清楚。研究肠道微生物群是否能调节醛固酮可以为了解微生物群如何影响血压提供新的视角。在这项研究中，我们旨在确定肠道微生物群是否能调节宿主的醛固酮。我们采用酶联免疫吸附试验（ELISAs）来评估肠道微生物群完整、受抑制或缺失的雌性和雄性小鼠的血浆醛固酮和血浆肾素活性（PRA）。此外，我们还检测了尿醛固酮。我们的研究结果表明，当抗生素治疗后肠道微生物群受到抑制时，雌性和雄性小鼠血浆和尿液中的醛固酮都会增加。相反，只有雄性小鼠的 PRA 增加。我们还发现，当肠道微生物群缺失时（无菌小鼠），血浆醛固酮会比常规动物显著增加（雌性和雄性），但 PRA 不会增加。了解肠道微生物群如何影响醛固酮水平可为高血压和/或原发性醛固酮增多症的发病和治疗提供有价值的见解。这些知识可能会为治疗干预开辟新的途径，如益生菌或饮食调整，以帮助通过基于微生物群的醛固酮变化来调节血压。
{"title":"Commensal Microbiota Regulate Aldosterone","authors":"Brittni N. Moore, Alexandra D. Medcalf, Rachel Q. Muir, Chudan Xu, Francine Z. Marques, Jennifer L. Pluznick","doi":"10.1152/ajprenal.00051.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00051.2024","url":null,"abstract":"The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We employed enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-free mice), plasma aldosterone is significantly increased compared to conventional animals (in both females and males), but PRA is not. Understanding how gut microbiota influence aldosterone levels could provide valuable insights into the development and treatment of hypertension and/or primary aldosteronism. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications to help regulate blood pressure via microbiota-based changes to aldosterone.","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00372.2023
Anjana Chaudhary, Zhibin He, Daniel J. Atwood, Makoto Miyazaki, Ozgur A. Oto, Allen Davidoff, Charles L. Edelstein
Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were 2 aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and Pkd1RC/RC mice, a hypomorphic Pkd1 gene model. In PCK rats and Pkd1RC/RC mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight and cyst index. Mechanisms of increased cyst growth that were investigated were pro-inflammatory cytokines, the inflammasome and crystal deposition in the kidney. Oxonic acid resulted in an increase in pro-inflammatory cytokines in the serum and kidney in Pkd1RC/RC mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In Pkd1RC/RC male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and Pkd1RC/RC mice. The effect is independent of inflammasome activation or crystal deposition in the kidney.
{"title":"Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models","authors":"Anjana Chaudhary, Zhibin He, Daniel J. Atwood, Makoto Miyazaki, Ozgur A. Oto, Allen Davidoff, Charles L. Edelstein","doi":"10.1152/ajprenal.00372.2023","DOIUrl":"https://doi.org/10.1152/ajprenal.00372.2023","url":null,"abstract":"Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were 2 aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and <i>Pkd1</i><sup>RC/RC</sup> mice, a hypomorphic <i>Pkd1</i> gene model. In PCK rats and <i>Pkd1</i><sup>RC/RC</sup> mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight and cyst index. Mechanisms of increased cyst growth that were investigated were pro-inflammatory cytokines, the inflammasome and crystal deposition in the kidney. Oxonic acid resulted in an increase in pro-inflammatory cytokines in the serum and kidney in <i>Pkd1</i><sup>RC/RC</sup> mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In <i>Pkd1</i><sup>RC/RC</sup> male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and <i>Pkd1</i><sup>RC/RC</sup> mice. The effect is independent of inflammasome activation or crystal deposition in the kidney.","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00027.2024
Evan C. Ray, Andrew Nickerson, Shaohu Sheng, Rolando Carrisoza-Gaytán, Tracey Lam, Allison Marciszyn, Lei Zhang, Alexa Jordahl, Chunming Bi, Aaliyah Winfrey, Zhaohui Kou, Sebastien Gingras, Annet Kirabo, Lisa M. Satlin, Thomas R. Kleyman
American Journal of Physiology-Renal Physiology, Ahead of Print.
美国生理学杂志-肾脏生理学》，提前出版。
{"title":"Influence of Proteolytic Cleavage of ENaC's Gamma Subunit upon Na+ and K+ Handling","authors":"Evan C. Ray, Andrew Nickerson, Shaohu Sheng, Rolando Carrisoza-Gaytán, Tracey Lam, Allison Marciszyn, Lei Zhang, Alexa Jordahl, Chunming Bi, Aaliyah Winfrey, Zhaohui Kou, Sebastien Gingras, Annet Kirabo, Lisa M. Satlin, Thomas R. Kleyman","doi":"10.1152/ajprenal.00027.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00027.2024","url":null,"abstract":"American Journal of Physiology-Renal Physiology, Ahead of Print. <br/>","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-18DOI: 10.1152/ajprenal.00378.2023
Brian Becknell, Mohammad El-Harakeh, Felipe Rodriguez-Tirado, Kelly M. Grounds, Birong Li, Macie Kercsmar, Xin Wang, Ashley R. Jackson
American Journal of Physiology-Renal Physiology, Ahead of Print.
美国生理学杂志-肾脏生理学》，提前出版。
{"title":"Keratin 5 Basal Cells are Temporally Regulated Developmental and Tissue Repair Progenitors in Bladder Urothelium","authors":"Brian Becknell, Mohammad El-Harakeh, Felipe Rodriguez-Tirado, Kelly M. Grounds, Birong Li, Macie Kercsmar, Xin Wang, Ashley R. Jackson","doi":"10.1152/ajprenal.00378.2023","DOIUrl":"https://doi.org/10.1152/ajprenal.00378.2023","url":null,"abstract":"American Journal of Physiology-Renal Physiology, Ahead of Print. <br/>","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affected by COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice four days after infection. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infected mice, along with the absence of MA10 in the kidneys, implied that the kidneys were affected by the MA10 infection-induced cytokine storm rather than by direct MA10 infection of the kidneys. RNA-sequencing analysis revealed that antiviral genes, such as the IFN/Janus kinase (JAK) pathway, were upregulated in MA10-infected kidneys. Upon administration of the JAK inhibitor baricitinib on days 1-3 after MA10 infection, an antiviral pathway was suppressed, and MA10 was detected more frequently in the kidneys. Notably, JAK inhibition upregulated the hypoxia response and exaggerated kidney injury. These results suggest that endogenous antiviral activity protects against SARS-CoV-2-induced kidney injury in the early phase of infection, providing valuable insights into the pathogenesis of COVID-19-associated nephropathy.
{"title":"JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice","authors":"Hibiki Sakai, Hiroyasu Kamuro, Nagisa Tokunoh, Takeshi Izawa, Shigeyuki Tamiya, Ayaha Yamamoto, Shota Tanaka, Daisuke Okuzaki, Chikako Ono, Yoshiharu Matsuura, Yoshiaki Okada, Yasuo Yoshioka, Yasushi Fujio, Masanori Obana","doi":"10.1152/ajprenal.00011.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00011.2024","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affected by COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice four days after infection. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infected mice, along with the absence of MA10 in the kidneys, implied that the kidneys were affected by the MA10 infection-induced cytokine storm rather than by direct MA10 infection of the kidneys. RNA-sequencing analysis revealed that antiviral genes, such as the IFN/Janus kinase (JAK) pathway, were upregulated in MA10-infected kidneys. Upon administration of the JAK inhibitor baricitinib on days 1-3 after MA10 infection, an antiviral pathway was suppressed, and MA10 was detected more frequently in the kidneys. Notably, JAK inhibition upregulated the hypoxia response and exaggerated kidney injury. These results suggest that endogenous antiviral activity protects against SARS-CoV-2-induced kidney injury in the early phase of infection, providing valuable insights into the pathogenesis of COVID-19-associated nephropathy.","PeriodicalId":7583,"journal":{"name":"American Journal of Physiology - Renal Physiology","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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