American Journal of Physiology - Renal Physiology最新文献_第2页

Succinylation of Park 7 Activates a Protective Metabolic Response to Acute Kidney Injury 公园 7 的琥珀酰化激活了对急性肾损伤的保护性代谢反应

American Journal of Physiology - Renal Physiology Pub Date : 2024-05-02 DOI: 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

{"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 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.","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}

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SGLT2 inhibitors: not every drug has the same effect SGLT2 抑制剂：并非每种药物都有相同的效果

American Journal of Physiology - Renal Physiology Pub Date : 2024-05-02 DOI: 10.1152/ajprenal.00126.2024

Alexander Staruschenko

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Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles DASH 饮食对尿液细胞外囊泡中钠离子-氯离子共转运体和 Aquaporin-2 的影响

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 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

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Double-negative T cells have a reparative role after experimental severe ischemic acute kidney injury 双阴性 T 细胞在实验性严重缺血性急性肾损伤后具有修复作用

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 10.1152/ajprenal.00376.2023

Kyungho Lee, Sepideh Gharaie, Johanna T. Kurzhagen, Andrea M. Newman-Rivera, Lois J. Arend, Sanjeev Noel, Hamid Rabb

{"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+ 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.","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}

引用次数: 0

Commensal Microbiota Regulate Aldosterone 共生微生物群调节醛固酮

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 10.1152/ajprenal.00051.2024

Brittni N. Moore, Alexandra D. Medcalf, Rachel Q. Muir, Chudan Xu, Francine Z. Marques, Jennifer L. Pluznick

{"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}

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Podocyte-Specific Silencing of Acid Sphingomyelinase Gene to Abrogate Hyperhomocysteinemia-Induced NLRP3 Inflammasome Activation and Glomerular Inflammation 抑制荚膜细胞特异性酸性鞘磷脂酶基因以消除高同型半胱氨酸血症诱导的 NLRP3 炎症小体激活和肾小球炎症

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 10.1152/ajprenal.00195.2023

Dandan Huang, Jason M. Kidd, Yao Zou, Xiaoyuan Wu, Ningjun Li, Todd W.B. Gehr, Pin-Lan Li, Guangbi Li

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Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models 在大鼠和小鼠模型中，用尿酸酶抑制剂提高血清尿酸会加重 PKD 的病情

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 10.1152/ajprenal.00372.2023

Anjana Chaudhary, Zhibin He, Daniel J. Atwood, Makoto Miyazaki, Ozgur A. Oto, Allen Davidoff, Charles L. Edelstein

{"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 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.","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}

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Influence of Proteolytic Cleavage of ENaC's Gamma Subunit upon Na+ and K+ Handling ENaC Gamma 亚基蛋白水解对 Na+ 和 K+ 处理的影响

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 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

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Keratin 5 Basal Cells are Temporally Regulated Developmental and Tissue Repair Progenitors in Bladder Urothelium 角蛋白 5 基底细胞是膀胱尿路上皮细胞中受时间调节的发育和组织修复祖细胞

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 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

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JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice 在小鼠感染 SARS-CoV-2 的早期阶段抑制 JAK 可抑制内源性抗病毒活性，从而加重肾损伤

American Journal of Physiology - Renal Physiology Pub Date : 2024-04-18 DOI: 10.1152/ajprenal.00011.2024

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

{"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}

引用次数: 0