American journal of physiology. Renal physiology最新文献

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A key role of AT1a receptors and Na+/H+ exchanger 3 in the proximal tubules in angiotensin II-induced and two-kidney, one-clip Goldblatt hypertension. 近端小管中AT1a受体和Na+/H+交换3在血管紧张素ii诱导的双肾单夹Goldblatt高血压中的关键作用
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-11-01 Epub Date: 2025-09-23 DOI: 10.1152/ajprenal.00122.2025
Xiao Chun Li, Rumana Hassan, Jia L Zhuo
{"title":"A key role of AT<sub>1a</sub> receptors and Na<sup>+</sup>/H<sup>+</sup> exchanger 3 in the proximal tubules in angiotensin II-induced and two-kidney, one-clip Goldblatt hypertension.","authors":"Xiao Chun Li, Rumana Hassan, Jia L Zhuo","doi":"10.1152/ajprenal.00122.2025","DOIUrl":"10.1152/ajprenal.00122.2025","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The present study tests the hypothesis that dual deletion of AT&lt;sub&gt;1a&lt;/sub&gt; receptors and Na&lt;sup&gt;+&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; exchanger 3 (NHE3) selectively in the proximal tubules further attenuates angiotensin II (Ang II)-induced and two-kidney, one-clip (2K1C) Goldblatt hypertension. Proximal tubule (PT)-specific AT&lt;sub&gt;1a&lt;/sub&gt; receptor and NHE3 double knockout mice, PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;/&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;, were generated using the iL-&lt;i&gt;Sglt2-Cre&lt;/i&gt;/&lt;i&gt;LoxP&lt;/i&gt; approach. Male and female wild-type (WT) and PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;/&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; double knockout mice were infused with a pressor dose of Ang II for 2 wk (1.5 mg/kg body wt/day ip) or induced with 2K1C Goldblatt hypertension for 4 wk. In wild-type (WT) mice, basal systolic blood pressure (SBP) was 118 ± 3 mmHg (&lt;i&gt;n&lt;/i&gt; = 9), which increased to 161 ± 3 mmHg in response to Ang II infusion (&lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;n&lt;/i&gt; = 10) or to 136 ± 3 mmHg in response to induction of 2K1C Goldblatt hypertension (&lt;i&gt;n&lt;/i&gt; = 12, &lt;i&gt;P&lt;/i&gt; &lt; 0.01). By comparison, basal SBP was 13 ± 2 mmHg lower in PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) or in PT-&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; single-gene knockout mice than WT mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). Double deletion of AT&lt;sub&gt;1a&lt;/sub&gt; and NHE3 in the proximal tubules further lowered basal SBP by 6 ± 2 mmHg in PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;/&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). In response to Ang II infusion, SBP increased to 121 ± 3 mmHg in PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;/PT-&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). 2K1C Goldblatt hypertension was attenuated in PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; (108 ± 3 mmHg, &lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;n&lt;/i&gt; = 10), PT-&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; (110 ± 2 mmHg, &lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;n&lt;/i&gt; = 10), or PT-&lt;i&gt;Agtr1a&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;/&lt;i&gt;Nhe3&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;/&lt;/sup&gt;&lt;i&gt;&lt;sup&gt;-&lt;/sup&gt;&lt;/i&gt; mice (103 ± 2 mmHg, &lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;n&lt;/i&gt; = 8), respectively. Taken together, our study provides further evidence for a key role of proximal tubule AT&lt;sub&gt;1a&lt;/sub&gt; receptors and NHE3 in the development of Ang II-induced and 2K1C Goldblatt hypertension.&lt;b&gt;NEW & NOTEWORTHY&lt;/b&gt; This study generates a novel mouse model with double deletion of AT&lt;sub&gt;1a&lt;/sub&gt; receptors and Na&lt;sup&gt;+&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; exchanger 3 (NHE3) in the proximal tubules to directly determine their role in the development of Ang II-induced and two-kidney, one-clip (2K1C) Goldblatt hypertension. This study provides further evidence for a key role of proximal tubule AT&lt;sub&gt;1a&lt;/sub&gt; receptor and NHE3 not only in maintaining physiological blood pressure homeostasis but also in t","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F589-F600"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133149","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
Diurnal function and expression of aquaporins in the mouse kidney. 小鼠肾脏水通道蛋白的日功能及表达。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-11-01 Epub Date: 2025-09-26 DOI: 10.1152/ajprenal.00162.2025
Hung Nguyen, Nha Van Huynh, Kelly A Hyndman
{"title":"Diurnal function and expression of aquaporins in the mouse kidney.","authors":"Hung Nguyen, Nha Van Huynh, Kelly A Hyndman","doi":"10.1152/ajprenal.00162.2025","DOIUrl":"10.1152/ajprenal.00162.2025","url":null,"abstract":"<p><p>Aquaporins (AQPs) are a family of water channels found throughout the body and in the kidney; they function in maintaining water homeostasis. The insertion of AQPs into the plasma membrane of the kidney cells drives water reabsorption back into the circulation, and the concentration of the urine involves AQP2 apical localization in the collecting duct principal cells. Kidney functions, like glomerular filtration rate (GFR) and urine flow, are significantly greater during the active period compared with the inactive period when sleeping. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality and that this reflects changes in kidney aquaporins in mice. Male and female C57BL/6J mice were studied in the middle of their active period [zeitgeber time (ZT) 18] or the middle of their inactive period (ZT6). We confirmed GFR was greater at ZT18 compared with ZT6. Urine and plasma osmolality were significantly greater at ZT18 in both sexes. Although ∼18% of kidney RNA had a diurnal pattern, the changes observed in the <i>Aqp</i> genes did not reflect protein abundance differences where nephron AQP1, AQP2, and AQP4 abundance were greater at ZT18 compared with ZT6. In conclusion, diurnal variability in plasma osmolality and urine-concentrating ability is likely driven by time-of-day changes in intake, greater GFR, and establishment of the medullary interstitial gradient during the active period. Greater nephron aquaporins in the middle of the active period may function to reabsorb water while the kidney excretes excess solutes to dilute the plasma osmolality and maintain fluid-electrolyte balance.<b>NEW & NOTEWORTHY</b> Mouse plasma and urine osmolalities are greater in the middle of the active period, when food/water intake, gut reabsorption, glomerular filtration rate, and urine flow are increased. There were time-of-day effects on aquaporin mRNA, and increased nephron abundance of aquaporins during the middle of the active period. As the kidneys excrete the excess solutes, the medullary interstitial gradient and aquaporins are primed to concentrate the urine and return the plasma osmolality to a steady state.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F601-F614"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180801","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
Renal tubular (pro)renin receptor deletion exacerbates kidney injury in db/db mice. 肾小管肾素受体缺失加重db/db小鼠肾损伤。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-14 DOI: 10.1152/ajprenal.00231.2025
Deborah Stuart, Caitlin S Peterson, Dhruvan Gopinath, Divya Sundar, Will Wheatley, Nirupama Ramkumar
{"title":"Renal tubular (pro)renin receptor deletion exacerbates kidney injury in db/db mice.","authors":"Deborah Stuart, Caitlin S Peterson, Dhruvan Gopinath, Divya Sundar, Will Wheatley, Nirupama Ramkumar","doi":"10.1152/ajprenal.00231.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00231.2025","url":null,"abstract":"<p><p>The (pro)renin receptor (PRR) is a multifunctional protein implicated in blood pressure regulation and kidney fibrosis. Previous studies report enhanced PRR expression in non-diabetic and diabetic kidney disease. In this study, we investigated whether deletion of renal tubular PRR attenuates kidney injury in type 2 diabetes. Floxed PRR mice were bred with mice expressing Pax8 rtTA and LC1 transgenes and db/db mice (B6.BKS) to obtain renal tubular PRR knockout (KO)-db/db mice. Male, age matched non-diabetic floxed controls, db/db mice and PRRKO-db/db mice were studied at 16, 20, 26 and 30 weeks of age. PRR KO mice were only studied at 30 weeks of age. To induce PRR deletion, PRR KO and PRRKO-db/db mice were treated with 2 mg/ml doxycycline for 12 days at 8-10 weeks of age. Compared to controls, db/db mice and PRRKO-db/db mice had higher body weights throughout the study and elevated blood glucose levels at weeks 16 and 20. Compared to controls and db/db mice, PRRKO-db/db mice had higher urine volume, water intake and urinary albumin excretion. At 30 weeks, kidney histology showed minimal tubular or glomerular injury among all 4 groups. PRR KO mice had elevated expression of tubular injury markers compared to the other 3 groups. Plasma sPRR levels were almost two-fold higher in diabetic mice relative to controls with no difference between db/db mice and PRR KO-db/db mice. Renal tubular deletion of PRR does not protect against kidney injury in type 2 diabetes; rather the loss of PRR impairs baseline tubular function which is exacerbated by type 2 diabetes.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294568","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
Acute Kidney Injury is Associated with Elevated Urinary Endotrophin. 急性肾损伤与尿内啡肽升高有关。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-13 DOI: 10.1152/ajprenal.00300.2025
Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir Parikh
{"title":"Acute Kidney Injury is Associated with Elevated Urinary Endotrophin.","authors":"Amanda J Clark, Brenda Mendoza Flores, Marie Christelle Saade, Kyle Q Vu, Isaac J Pence, Ningyan Zhang, Zhiqiang An, Dawei Bu, Philipp E Scherer, Samir Parikh","doi":"10.1152/ajprenal.00300.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00300.2025","url":null,"abstract":"<p><p><b>Background:</b> Acute Kidney Injury (AKI) is prevalent among hospitalized patients. Novel biomarkers are needed to diagnose AKI and target therapies. Endotrophin (ETP) is a molecule released during collagen type VI formation that may promote injury and fibrosis. While serum ETP elevation has been associated with adverse outcomes in AKI, urinary ETP has not been assessed in AKI nor has ETP been evaluated in a pediatric population. <b>Methods:</b> Urine samples were collected from a tertiary children's hospital. Medical records were reviewed and patients who met criteria were sorted into 3 categories: 1. AKI; 2. Hospitalized controls; and 3. Outpatient controls. ETP was measured using ELISA, and results were corrected to urine creatinine (uETP:Cre). A multivariate linear regression assessed whether demographic variables independently associated with uETP:Cre. Odds of AKI were assessed in serial uETP:Cre tertiles using a multivariate logistic regression model that adjusted for patient variables. <b>Results:</b> uETP:Cre was elevated in patients with AKI compared to hospitalized patients without AKI (p<0.05) and outpatient controls (p<0.0001). Multivariate analysis revealed that age, but not sex, race, or ethnicity independently correlated with uETP:Cre. After adjustment for these variables, the odds ratio for AKI increased with serial uETP:Cre tertiles. <b>Conclusions:</b> Non-invasive measurement of uETP may deliver meaningful information to aid AKI diagnosis. Given that ETP may be both a biomarker and a clinically actionable stimulus of inflammation and fibrosis, future studies are needed to understand the role of elevated ETP in AKI and if existing ETP neutralizing antibodies could represent a new avenue of AKI therapy.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287944","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
Regional metabolic analysis of structurally preserved kidney slices by ex vivo respirometry. 体外呼吸法分析结构保存肾片的区域代谢。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-10 DOI: 10.1152/ajprenal.00157.2025
Ryoichi Bessho, Olena Davidoff, Hanako Kobayashi, Volker Hans Haase
{"title":"Regional metabolic analysis of structurally preserved kidney slices by ex vivo respirometry.","authors":"Ryoichi Bessho, Olena Davidoff, Hanako Kobayashi, Volker Hans Haase","doi":"10.1152/ajprenal.00157.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00157.2025","url":null,"abstract":"<p><p>A comprehensive spatial analysis of kidney metabolism is essential for advancing knowledge of both normal kidney physiology and pathophysiology. The kidney exhibits marked regional differences in bioenergetic demands and substrate utilization, reflecting the distinct functional profiles of each nephron segment. To complement existing approaches with freshly isolated tubules or primary cell cultures, we established and validated an <i>ex vivo</i> respirometry method using structurally preserved kidney slices on a Seahorse XFe24 platform. This protocol avoids tissue disruption or enzymatic digestion and enables simultaneous, region-specific measurements of metabolic fluxes in the cortex, outer medulla, and inner medulla. It provides an integrated readout of the metabolic properties of the cell types present within each anatomical region. We demonstrate the utility of this approach through proof-of-principle studies that profile region-specific metabolic fluxes under hyperglycemic conditions in a mouse model of obesity and type 2 diabetes, as well as the metabolic alterations that accompany the transition from acute ischemic injury to chronic kidney disease. Furthermore, to highlight its relevance for therapeutic discovery, we applied this method to assess the impact of pharmacological hypoxia-inducible factor (HIF) activation on regional kidney bioenergetics. In summary, this protocol advances the study of kidney metabolism by providing a robust platform for region-specific analysis of kidney respiration and bioenergetics and holds promise for accelerating the development of novel therapies targeting metabolic pathways in kidney disease.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276735","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
5-hydroxytryptamine 1F receptor loss reduces renal vasculature and prevents lasmiditan-induced recovery following moderate-severe acute kidney injury in mice. 5-羟色胺1F受体丧失可减少肾血管,并阻止小鼠中重度急性肾损伤后拉斯米坦诱导的恢复。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-08 DOI: 10.1152/ajprenal.00307.2025
Austin D Thompson, Kai W McAlister, Natalie E Scholpa, Jaroslav Janda, John Hortareas, Teodora G Georgieva, Rick G Schnellmann
{"title":"5-hydroxytryptamine 1F receptor loss reduces renal vasculature and prevents lasmiditan-induced recovery following moderate-severe acute kidney injury in mice.","authors":"Austin D Thompson, Kai W McAlister, Natalie E Scholpa, Jaroslav Janda, John Hortareas, Teodora G Georgieva, Rick G Schnellmann","doi":"10.1152/ajprenal.00307.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00307.2025","url":null,"abstract":"<p><p>Kidney disease (KD) has emerged as a major global health crisis and leading cause of morbidity and mortality worldwide, impacting over 850 million individuals. Pathophysiological hallmarks of KD encompass renal tubular cell injury/necrosis, tubulointerstitial fibrosis, vascular dysfunction/rarefaction, and mitochondrial dysfunction, all of which are implicated in disease initiation/progression. Unfortunately, there remains a general lack of effective FDA-approved therapeutics for the treatment of KD. Thus, the identification of novel and/or repurposed treatment strategies remains of dire importance. Previously, we identified the 5-hydroxytryptamine 1F receptor (HTR1F) as a modulator of renal mitochondrial homeostasis, and demonstrated that mice lacking this receptor exhibit hindered renal recovery following mild ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Additionally, we reported that treatment with the HTR1F agonist lasmiditan, an FDA approved therapeutic for acute migraines, expedites renal recovery following I/R-AKI in mice. Here, we show that lasmiditan treatment following moderate-severe I/R-AKI ameliorates acute tubular injury, mitochondrial dysfunction, tubulointerstitial fibrosis, and vascular rarefaction in the renal cortex of mice, which likely contributes to the enhanced recovery observed. Importantly, we also confirm that this lasmiditan-induced renal recovery is contingent on <i>HTR1F</i> expression. Furthermore, mice lacking the HTR1F exhibit decreased innate renal cortical vasculature, exacerbated rarefaction, and markedly increased mortality rates following moderate-severe I/R-AKI. These findings not only underscore the importance of <i>HTR1F</i> expression and agonism in renal repair and recovery, but also further highlight the repurposing potential of lasmiditan for the treatment of AKI and/or KD onset/progression.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254004","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
Pregnane X receptor (PXR) increases urine concentration by upregulating hypothalamic arginine vasopressin expression. 孕激素X受体(PXR)通过上调下丘脑精氨酸抗利尿素的表达而增加尿浓度。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-06 DOI: 10.1152/ajprenal.00187.2025
Xiaowan Sun, Ruifen Li, Zhilin Luan, Beibei Ma, Hu Xu, Taotao Luo, Yitong Hu, Wenqian Zhao, Rongfang Qiao, Chunxiu Du, Jiahui Cao, Hui Zhou, Yanlin Guo, Jin Zhong, Yufei Zhang, Bin Yang, Youfei Guan, Xiao-Yan Zhang
{"title":"Pregnane X receptor (PXR) increases urine concentration by upregulating hypothalamic arginine vasopressin expression.","authors":"Xiaowan Sun, Ruifen Li, Zhilin Luan, Beibei Ma, Hu Xu, Taotao Luo, Yitong Hu, Wenqian Zhao, Rongfang Qiao, Chunxiu Du, Jiahui Cao, Hui Zhou, Yanlin Guo, Jin Zhong, Yufei Zhang, Bin Yang, Youfei Guan, Xiao-Yan Zhang","doi":"10.1152/ajprenal.00187.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00187.2025","url":null,"abstract":"<p><p>The pregnane X receptor (PXR) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. PXR is constitutively expressed in the hypothalamus and kidney, with its physiological function incompletely understood. In this study, we found that treatment with pregnenolone-16α-carbonitrile (PCN), an endogenous PXR ligand, significantly reduced urine volume and increased urine osmolarity in C57BL/6 mice. In contrast, PXR gene knockout (PXR<sup>-/-</sup>) mice exhibited impaired urine-concentrating ability, leading to a polyuria phenotype. Additionally, treatment of mice with PCN is significantly upregulated, while PXR gene deficiency substantially reduced, arginine vasopressin (AVP) expression in the hypothalamus. Bioinformatic analysis showed that the mouse AVP gene promoter contains a putative PXR response element (PXRE). The luciferase reporter, ChIP and EMSA assays further revealed that PXR can bind to the PXRE, resulting in a significant increase in AVP gene transcription. Collectively, the present study demonstrates that hypothalamic PXR plays a critical role in regulating urine volume, and its activation enhances urinary concentrating capacity primarily by up regulating the expression of AVP in the hypothalamus.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240537","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
Decreased parietal epithelial cell density is linked to podocyte depletion and predictors of kidney disease progression in human kidneys. 壁上皮细胞密度降低与足细胞耗竭和人类肾脏疾病进展的预测因子有关。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-06 DOI: 10.1152/ajprenal.00243.2025
Jenna T Ference-Salo, Christopher L O'Connor, Rajasree Menon, Edgar A Otto, Meghan Dailey, Markus Bitzer, Jeffrey A Beamish
{"title":"Decreased parietal epithelial cell density is linked to podocyte depletion and predictors of kidney disease progression in human kidneys.","authors":"Jenna T Ference-Salo, Christopher L O'Connor, Rajasree Menon, Edgar A Otto, Meghan Dailey, Markus Bitzer, Jeffrey A Beamish","doi":"10.1152/ajprenal.00243.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00243.2025","url":null,"abstract":"<p><p>Parietal epithelial cells (PECs) have been implicated in the pathogenesis of glomerulosclerosis in rodent models, and novel technologies are beginning to unravel their contributions to human glomerular disease. Here we report the development, validation, and application of a deep learning approach to analyze the PEC population in over 14,000 glomeruli from nephrectomy samples from patients with minimal overt chronic kidney disease (CKD). This analysis revealed a striking correlation between PEC density and podocyte density. Reduced PEC density also was associated with aging and the presence of diabetes. Furthermore, the PEC density in normal-appearing glomeruli was associated with the frequency of glomerular pathology, including global and segmental glomerulosclerosis, in the same patient sample. Patients with low PEC density had gene expression changes consistent with cellular stress in PECs. These observations support a link between PEC population and the progression of CKD.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240526","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
Inducible Avp Knockout Mouse Line. 诱导Avp敲除小鼠系。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-06 DOI: 10.1152/ajprenal.00340.2025
Shaza Khan, Lihe Chen, Chung-Lin Chou, Syed J Khundmiri, Mark A Knepper
{"title":"Inducible <i>Avp</i> Knockout Mouse Line.","authors":"Shaza Khan, Lihe Chen, Chung-Lin Chou, Syed J Khundmiri, Mark A Knepper","doi":"10.1152/ajprenal.00340.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00340.2025","url":null,"abstract":"<p><p>Arginine vasopressin (AVP) is a peptide hormone synthesized in the hypothalamus and secreted by the posterior pituitary. Previous studies toward understanding of AVP physiology relied heavily on Brattleboro rats, which have a spontaneous mutation in the <i>Avp</i> gene and lack circulating AVP. However, these rats are difficult to breed due to high neonatal death and behavioral issues, causing commercial breeders to stop production. To address this, we developed a mouse line with tamoxifen-inducible deletion of <i>Avp</i>. We used CRISPR/Cas9 to insert loxP sites into the <i>Avp</i> gene. These mice were then bred with mice expressing a tamoxifen-inducible Cre recombinase. The resulting conditional knockout mice (<i>Avp</i><sup>flx/flx</sup>Cre<sup>+</sup>) are viable, fertile, and healthy before induction. Administration of tamoxifen in 8-12 week-old mice successfully deleted <i>Avp</i>, as confirmed by Sanger sequencing. This deletion caused a significant decrease in urine osmolality, a hallmark of AVP deficiency. The kidney structure remained normal, with no signs of medullary atrophy. Additionally, these mice exhibited substantial decreased expression of AQP2, which is involved in water reabsorption in the kidney inner medulla. We illustrate the use of this model by using RNA-seq to profile the consequences of <i>Avp</i> deletion on gene expression in the kidney. The curated RNA-seq data can be browsed, searched or downloaded at https://esbl.nhlbi.nih.gov/Databases/AVP-KO/. In conclusion, we successfully created an inducible <i>Avp</i> knockout mouse line that has been made available to the research community. This model will be valuable for studying water balance regulation, polycystic kidney disease, and the neural, vascular, and metabolic functions of vasopressin.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240584","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
Pannexin channels in the kidney. 肾内联蛋白通道。
IF 3.4
American journal of physiology. Renal physiology Pub Date : 2025-10-03 DOI: 10.1152/ajprenal.00259.2025
Madison Williams, Brooke O'Donnell, Linda Columbus, Leon Delalio, Uta Erdbrügger, Brant E Isakson
{"title":"Pannexin channels in the kidney.","authors":"Madison Williams, Brooke O'Donnell, Linda Columbus, Leon Delalio, Uta Erdbrügger, Brant E Isakson","doi":"10.1152/ajprenal.00259.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00259.2025","url":null,"abstract":"<p><p>Renal dysfunction leads to critical health conditions, including acute kidney injury (AKI) and chronic kidney disease (CKD), and is a driver of hypertension. Despite their global prevalence and impact, the pathophysiology for all kidney disease subtypes is incompletely understood, therefore, many patients progress to kidney failure, needing dialysis and transplantation. This review highlights the role of pannexins-a family of channel-forming glycoproteins-in renal physiology and pathophysiology. Compared to other organ systems such as the brain and cardiovascular system, relatively little is known about the function of pannexins in the kidney. However, recent findings indicate that pannexins may be potential therapeutic targets in the treatment of hypertension, AKI, and CKD, though further research is needed to fully understand their precise role in renal health and disease.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226472","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
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