American journal of physiology. Renal physiology最新文献_第2页

Local C1q/TNF-related protein 1 attenuates kidney inflammation and fibrosis by regulating macrophage activation. 局部C1q/ tnf相关蛋白1通过调节巨噬细胞活化减轻肾脏炎症和纤维化。

American journal of physiology. Renal physiology Pub Date : 2025-05-27 DOI: 10.1152/ajprenal.00346.2024

Fei Wang, Zhe Gong, Nianjia Yang, Gang Zhou, Mengxue Jia, Wenjin Liu, Huaqing Zheng, Guangyu Bi, Ye Feng

{"title":"Local C1q/TNF-related protein 1 attenuates kidney inflammation and fibrosis by regulating macrophage activation.","authors":"Fei Wang, Zhe Gong, Nianjia Yang, Gang Zhou, Mengxue Jia, Wenjin Liu, Huaqing Zheng, Guangyu Bi, Ye Feng","doi":"10.1152/ajprenal.00346.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00346.2024","url":null,"abstract":"Chronic kidney disease (CKD), characterized by persistent inflammation and progressive renal fibrosis, remains a major therapeutic challenge due to incomplete understanding of its pathogenesis. Since C1q/TNF-related protein 1 (CTRP1) plays a potential role in fibrosis and inflammation in other tissues, we investigated the role of CTRP1 in patients and mice with CKD. Here CTRP1 expression was increased in plasma and decreased in kidneys from patients with CKD. Upregulation of renal CTRP1 with adeno-associated-CTRP1 were associated with decreased renal fibrosis, inflammation, macrophage accumulation and activation in mice models. Mechanistically, CTRP1 abolished the expression of TGFß1-induced macrophage M2-associated genes and the transcriptional regulators Yes-associated protein Yap)/transcriptional coactivator with PDZ-binding motif (Taz). Additionally, upregulation of CTRP1 could partly down regulate LPS-stimulated expression of pro inflammatory genes in vitro. Conditioned media from TGFß1-CTRP1-pretreated macrophages could less efficiently stimulate fibroblast activation compared to those from TGFß1-pretreated macrophages. Thus, our study reveals local CTRP1 as a potential regulator of chronic inflammation and kidney fibrosis through regulating macrophage activation. Taking together, these findings support renal CTRP1 as a novel therapeutic target for CKD.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164290","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

Early renal response to long term salt loading: Mitochondrial dysfunction, ER stress and uromodulin accumulation in the kidney medulla. 长期盐负荷的早期肾脏反应：线粒体功能障碍、内质网应激和肾髓质的尿调蛋白积累。

American journal of physiology. Renal physiology Pub Date : 2025-05-27 DOI: 10.1152/ajprenal.00348.2024

Humaira Parveen, Philipp Boder, William Mullen, Delyth Graham, Tom Van Agtmael, Luca Rampoldi, Christian Delles, Sheon Mary

{"title":"Early renal response to long term salt loading: Mitochondrial dysfunction, ER stress and uromodulin accumulation in the kidney medulla.","authors":"Humaira Parveen, Philipp Boder, William Mullen, Delyth Graham, Tom Van Agtmael, Luca Rampoldi, Christian Delles, Sheon Mary","doi":"10.1152/ajprenal.00348.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00348.2024","url":null,"abstract":"Kidneys play a critical role in maintaining water and electrolyte balance, but prolonged salt loading can disrupt renal function by inducing osmotic and oxidative stress. While high salt intake is well-known to contribute to hypertension and kidney damage, the early renal responses to mild, long-term salt intake, particularly in normotensive individuals, remain poorly understood. To help address this knowledge gap, we investigated the effects of exposing normotensive Wistar Kyoto (WKY) rats to 1% NaCl over a 3-month period, focusing on the medullary region and the adaptive cellular mechanisms in response to salt-induced stress. Additionally, we examined the acute effects of 4 hours of salt exposure on medullary tubules. The long-term salt intake did not significantly alter blood pressure or cause notable kidney damage, but did lead to differential expression of proteins associated with mitochondrial dysfunction and ER stress in the renal medulla. Acute 4-hour salt exposure triggered a rapid cellular response involving proteins linked to mitochondrial activity and oxidative stress responses. Both acute and chronic settings significantly reduced UMOD excretion with altered trafficking indicating intracellular accumulation within medullary cells. This provides evidence that chronic salt loading disrupts normal protein handling without immediate renal injury, shedding light on adaptive mechanisms in the kidney to mitigate osmotic stress. These early adaptations provide insight into the mechanisms underlying salt-related renal pathologies and may inform therapeutic strategies for individuals susceptible to the effects of dietary salt.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164288","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

Gliflozins in Hypertension: Basic Mechanisms and Clinical Insights. 格列净治疗高血压：基本机制和临床见解。

American journal of physiology. Renal physiology Pub Date : 2025-05-27 DOI: 10.1152/ajprenal.00119.2025

Timo Rieg, Ruisheng Liu, Alexander Staruschenko

{"title":"Gliflozins in Hypertension: Basic Mechanisms and Clinical Insights.","authors":"Timo Rieg, Ruisheng Liu, Alexander Staruschenko","doi":"10.1152/ajprenal.00119.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00119.2025","url":null,"abstract":"Sodium-glucose cotransport (SGLT) inhibitors, or gliflozins, initially developed for managing type 2 diabetes mellitus, have emerged as promising therapeutic agents for hypertension, offering both cardiovascular and renal protection. Recently, a dual SGLT1/SGLT2 inhibitor was approved for the treatment of heart failure (HF), including preserved and reduced ejection fraction. Clinical trials consistently demonstrate the ability of gliflozins to lower blood pressure (BP) and reduce cardiovascular events, particularly in patients with comorbid conditions such as chronic kidney disease and HF. However, these trials typically include hypertension as a comorbidity rather than as the primary condition under investigation, and data specific to hypertensive patients without diabetes mellitus remain limited. This review highlights recent clinical and basic mechanistic insights into the antihypertensive effects of gliflozins. We discuss their influence on BP regulation, including modulation of renal sodium handling, the renin angiotensin-aldosterone system, and vascular function. Additionally, gliflozins exhibit significant anti-inflammatory and anti-fibrotic properties, reducing the risk of organ damage associated with chronic hypertension. Their metabolic benefits extend beyond glucose control, contributing to weight loss, and reduced uric acid levels, collectively supporting better cardiovascular outcomes. Accordingly, we also provide a brief overview of these metabolic effects. As ongoing research continues to explore the broader therapeutic applications of gliflozins, these agents may become integral to the management of hypertension, particularly in patients with complex cardiovascular and renal conditions.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153035","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

Multiparametric quantitative magnetic resonance imaging of skeletal muscle in CKD. CKD骨骼肌多参数定量磁共振成像。

American journal of physiology. Renal physiology Pub Date : 2025-05-27 DOI: 10.1152/ajprenal.00254.2024

Noah Markewitz, Can Wu, Moriel Vandsburger, William Paredes, Sally Duran, Saisha Islam, Brian Noehren, Christopher S Fry, Qi Peng, Matthew K Abramowitz

{"title":"Multiparametric quantitative magnetic resonance imaging of skeletal muscle in CKD.","authors":"Noah Markewitz, Can Wu, Moriel Vandsburger, William Paredes, Sally Duran, Saisha Islam, Brian Noehren, Christopher S Fry, Qi Peng, Matthew K Abramowitz","doi":"10.1152/ajprenal.00254.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00254.2024","url":null,"abstract":"Skeletal muscle dysfunction causes functional decline and disability in patients with chronic kidney disease (CKD). Identification of muscle pathology prior to significant loss of physical function would be a major advance. Multiparametric, quantitative magnetic resonance imaging (qMRI) of 7 leg muscle groups (3 thigh, 4 calf) was conducted in patients with CKD stages 4-5 (n=6), end-stage kidney disease (ESKD, n=3), and healthy controls (n=10) using a 3 Tesla MRI scanner. Measurements included T1 relaxation time in the rotating frame (T1ρ) and transverse relaxation time (T2) mapping, Dixon imaging of intramuscular fat content, diffusion tensor imaging (DTI) for muscle structure, and 1H-MR spectroscopy for intra- and extra-myocellular lipid (IMCL and EMCL, respectively) and physiologically relevant muscle metabolites. T1ρ and T2 times were prolonged and fat fraction (FF) was higher in CKD patients compared with controls (differences of 4.99 ms (95% CI 1.71-8.27), 6.72 ms (95% CI 3.78-9.66), and 6.67% (95% CI 0.65-12.68), respectively). T1ρ and FF were similarly elevated across muscle groups, whereas T2 differences may have been greater in calf muscles. T1ρ and T2 were lower in ESKD patients compared with CKD and similar to controls, consistent with prior histologic assessment of muscle fibrosis. No significant differences by CKD status were observed for DTI parameters. Compared with controls, IMCL was higher in CKD patients and trimethylamine and creatine concentrations were lower. In sum, multiparametric qMRI of skeletal muscle in CKD patients non-invasively identified differences in metrics associated with fibrosis, fat infiltration, and metabolic dysregulation.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153053","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

Vasopressin V1a and V1b receptor antagonism does not affect the efficacy of tolvaptan in Polycystic Kidney Disease. 抗利尿激素V1a和V1b受体拮抗剂不影响托伐普坦治疗多囊肾病的疗效。

American journal of physiology. Renal physiology Pub Date : 2025-05-26 DOI: 10.1152/ajprenal.00350.2024

Xiaofang Wang, Li Jiang, Kavini Nanayakkara, Jinghua Hu, Vicente E Torres

{"title":"Vasopressin V1a and V1b receptor antagonism does not affect the efficacy of tolvaptan in Polycystic Kidney Disease.","authors":"Xiaofang Wang, Li Jiang, Kavini Nanayakkara, Jinghua Hu, Vicente E Torres","doi":"10.1152/ajprenal.00350.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00350.2024","url":null,"abstract":"Vasopressin plays a major role in the pathogenesis of autosomal dominant polycystic kidney disease (PKD), the fourth leading cause of end-stage kidney disease. The vasopressin V2 receptor (V2R) antagonist tolvaptan is the only approved treatment. The role of vasopressin V1a and V1b receptors (V1aR, V1bR) has not been studied. Pkd1RC/RC mice were allocated to control, and 5 experimental groups treated with tolvaptan, OPC21268 (V1aR antagonist), SSR149415 (V1bR antagonist), tolvaptan plus OPC21268 or tolvaptan plus SSR149415, from 4 to 16 weeks of age, to compare their separate effects on PKD and to determine whether addition of OPC21268 or SSR149415 potentiates or hinders the therapeutic effect of tolvaptan. Tolvaptan significantly reduced total kidney volume (TKV) measured by MRI and rate of TKV growth. OPC21268 had no effect on PKD when administered alone. SSR149415 reduced TKV and TKV growth in female mice only. The sex dependent effect may be due to the increased expression of the V2 and V1b receptors in the kidneys of female compared to male Pkd1RC/RC mice. When OPC21268 or SSR149415 were administered in combination with tolvaptan, TKV, TKV growth, kidney weights, kidney weights adjusted by body weight, cyst indices and volumes, and plasma urea concentrations were not different from those observed with administration of tolvaptan alone. These results indicate that the beneficial effects of tolvaptan in PKD are mainly mediated by the inhibition of V2 receptors and provide no support for clinical trials of V2R antagonists combined with either V1a or V1b receptor antagonists.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144380","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

Logic-Based Modeling of Inflammatory Macrophage Crosstalk with Glomerular Endothelial Cells in Diabetic Kidney Disease. 糖尿病肾病中炎性巨噬细胞与肾小球内皮细胞串扰的逻辑建模

American journal of physiology. Renal physiology Pub Date : 2025-05-26 DOI: 10.1152/ajprenal.00362.2024

Krutika Patidar, Ashlee N Ford Versypt

{"title":"Logic-Based Modeling of Inflammatory Macrophage Crosstalk with Glomerular Endothelial Cells in Diabetic Kidney Disease.","authors":"Krutika Patidar, Ashlee N Ford Versypt","doi":"10.1152/ajprenal.00362.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00362.2024","url":null,"abstract":"Diabetic kidney disease is a complication in one out of three patients with diabetes. Aberrant glucose metabolism in diabetes leads to structural and functional damage in glomerular tissue and a systemic inflammatory immune response. Complex cellular signaling is at the core of metabolic and functional derangement. Unfortunately, the mechanism underlying the role of inflammation in glomerular endothelial cell dysfunction during diabetic kidney disease is not fully understood. Mathematical models in systems biology allow the integration of experimental evidence and cellular signaling networks to understand mechanisms involved in disease progression. This study developed a logic-based ordinary differential equations model to study inflammatory crosstalk between macrophages and glomerular endothelial cells during diabetic kidney disease progression using a protein signaling network stimulated with glucose and lipopolysaccharide. This modeling approach reduced the biological parameters needed to study signaling networks. The model was fitted to and validated against available biochemical data from in vitro experiments. The model identified mechanisms for dysregulated signaling in macrophages and glomerular endothelial cells during diabetic kidney disease. In addition, the influence of signaling interactions on glomerular endothelial cell morphology through selective knockdown and downregulation was investigated. Simulation results showed that partial knockdown of VEGF receptor 1, PLC-γ, adherens junction proteins, and calcium partially improved intercellular junction integrity between glomerular endothelial cells. These findings contribute to understanding signaling and molecular perturbations that affect the glomerular endothelial cells in the early stage of diabetic kidney disease.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144924","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 G Protein-coupled Estrogen Receptor 1 Regulates the Epithelial Sodium Channel Promoting Natriuresis to a Greater Extent in Females. 肾G蛋白偶联雌激素受体1调节上皮钠通道在更大程度上促进女性尿钠

American journal of physiology. Renal physiology Pub Date : 2025-05-22 DOI: 10.1152/ajprenal.00019.2025

Victoria L Nasci, Jean Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh Pochynyuk, James D Stockand, Eman Y Gohar

{"title":"Renal G Protein-coupled Estrogen Receptor 1 Regulates the Epithelial Sodium Channel Promoting Natriuresis to a Greater Extent in Females.","authors":"Victoria L Nasci, Jean Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh Pochynyuk, James D Stockand, Eman Y Gohar","doi":"10.1152/ajprenal.00019.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00019.2025","url":null,"abstract":"Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat renal tubules in a sex and region-specific manner. Within the renal medulla, the number of ENaC/GPER1-positive tubules was greater in females than males. Renal medullary inhibition of ENaC or activation of GPER1 evoked comparable natriuresis in female rats. Electrophysiology revealed that pharmacologic GPER1 activation downregulated ENaC activity, whereas genetic deletion of GPER1 from the principal cells of the collecting duct caused ENaC hyperactivity. The hyperactivity of ENaC caused by deletion of GPER1 in the principal cells was greater in female than male mice. RNAscope co-expression of AQP2 and GPER1 confirmed the KO of GPER1 from the PCs in the kidney. Thus, renal GPER1 functionally interacts with ENaC in a sex-specific manner to promote natriuresis.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129752","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

Identification and Localization of Adhesion G Protein-Coupled Receptor Expression in the Murine Kidney. 小鼠肾脏中粘附G蛋白偶联受体表达的鉴定和定位。

American journal of physiology. Renal physiology Pub Date : 2025-05-15 DOI: 10.1152/ajprenal.00134.2025

Hailey Steichen, Jianxiang Xue, Nathan A Zaidman

{"title":"Identification and Localization of Adhesion G Protein-Coupled Receptor Expression in the Murine Kidney.","authors":"Hailey Steichen, Jianxiang Xue, Nathan A Zaidman","doi":"10.1152/ajprenal.00134.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00134.2025","url":null,"abstract":"Adhesion G protein-coupled receptors (AGPCRs) are a class of seven-transmembrane receptors that sense cell-to-cell and cell-to-extracellular matrix transient adhesive events. AGPCRs are physiologically relevant and regulate processes throughout the body. However, the physiological roles of many AGPCRs are undefined. Unlike GPCRs that bind soluble agonists, AGPCRs uniquely depend on extracellular interactions and stimuli to facilitate endogenous activation by a tethered peptide agonist. Therefore, it is paramount to determine the cellular localization of AGPCRs to begin unraveling their functional roles. In the present work, we have identified the most abundant AGPCRs expressed in the murine kidney and determined their cellular localization through a combination of single-nucleus RNA sequencing and RNAscope fluorescent in situ hybridization. We report the transcriptional abundance of six AGPCRs that are expressed in a cell-specific manner, but also demonstrate that Adgrf1, a receptor with low but specific abundance by snRNAseq, is detected in a subset of principal cells by RNAscope. Additionally, we identify cell-specific transcript variants of Adgrf5 in the kidney, supporting a significant role of alternative splicing in AGPCR physiology. These data will assist in the generation of tissue- and cell-specific hypotheses and enable future investigations into the physiological roles of AGPCRs in the kidney and other tissues.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082751","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

Knockout of the V-ATPase interacting protein Tldc2 in B-type kidney intercalated cells impairs urine alkalinization. 敲除b型肾插层细胞中v - atp酶相互作用蛋白Tldc2可损害尿碱化。

American journal of physiology. Renal physiology Pub Date : 2025-05-13 DOI: 10.1152/ajprenal.00363.2024

Amity F Eaton, Elizabeth C Danielson, Leona J Tu, Dennis Brown, Maria Merkulova

{"title":"Knockout of the V-ATPase interacting protein Tldc2 in B-type kidney intercalated cells impairs urine alkalinization.","authors":"Amity F Eaton, Elizabeth C Danielson, Leona J Tu, Dennis Brown, Maria Merkulova","doi":"10.1152/ajprenal.00363.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00363.2024","url":null,"abstract":"Intercalated cells (ICs) are acid-base regulatory cells in the kidney collecting duct that excrete either acid or base into the urine in response to systemic cues. A-ICs deliver protons into the tubule lumen via an apical proton pump (V-ATPase) and reabsorb base (bicarbonate) using the AE1 anion exchanger. B-ICs function in the opposite direction. They have basolateral V-ATPase and secrete bicarbonate into the lumen via the anion exchange protein, pendrin. The function of a third IC subtype, the non-A non-B IC which has apical pendrin and apical V-ATPase, is less well understood. We previously reported that members of the TLDc protein family interact with the V-ATPase and may regulate its function. TLDc proteins exhibit a distinct expression pattern in the kidney with RNAseq showing high, differential expression of Tldc2 in B-ICs. Here, we show by RNAscope imaging that Tldc2 is indeed expressed in B-ICs, but also in some non-A, non-B ICs. Using Tldc2 knockout (Tldc2-/-) mice, we found that males and females had significantly lower urine pH than wild-type littermates, and their ability to increase urine pH in response to a bicarbonate load was impaired. In addition, Tldc2-/- males developed hyperbicarbonatemia. Tldc2-/- kidneys contained fewer B-ICs than wild-type mice, but they were replaced by more non-A, non-B ICs; the number of A-ICs was unchanged. Finally, there was decreased basolateral accumulation of V-ATPase in Tldc2-/- B-ICs. These findings suggest that Tldc2 is a novel gene involved in renal acid-base regulation and in addition, may serve as a differentiation marker for B-ICs.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002037","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

Altered renal vascular patterning reduces ischemic kidney injury and limits age-associated vascular loss. 肾血管模式改变可减少缺血性肾损伤并限制年龄相关的血管损失。

American journal of physiology. Renal physiology Pub Date : 2025-05-07 DOI: 10.1152/ajprenal.00284.2024

Sarah R McLarnon, Samuel E Honeycutt, Pierre-Emmanuel Y N'Guetta, Yubin Xiong, Xinwei Li, Koki Abe, Hiroki Kitai, Tomokazu Souma, Lori L O'Brien

{"title":"Altered renal vascular patterning reduces ischemic kidney injury and limits age-associated vascular loss.","authors":"Sarah R McLarnon, Samuel E Honeycutt, Pierre-Emmanuel Y N'Guetta, Yubin Xiong, Xinwei Li, Koki Abe, Hiroki Kitai, Tomokazu Souma, Lori L O'Brien","doi":"10.1152/ajprenal.00284.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00284.2024","url":null,"abstract":"The kidney vasculature has a complex arrangement, which runs in both series and parallel to perfuse the renal tissue and appropriately filter plasma. Recent studies have demonstrated that the development of this vascular pattern is dependent on netrin-1 secreted by renal stromal progenitors. Mice lacking netrin-1 (Ntn1) from these cells develop an arterial tree with stochastic branching, particularly of the large interlobar vessels. The current study investigated whether abnormalities in renal vascular pattern altered kidney function or response to injury. To examine this, we analyzed kidney function at baseline as well as in response to recovery from a model of bilateral ischemic injury and measured vascular dynamics in 7- to 8-month-old mice. We found no differences in kidney function or morphology at baseline between mice with an abnormal arterial pattern compared to control. Interestingly, male and female mutant mice with stochastic vascular patterning showed a reduction in tubular injury in response to ischemia. Similarly, mutant mice also had a preservation of perfused vasculature with increased age compared to a reduction in the control group. These results suggest that guided and organized patterning of the renal vasculature may not be required for normal kidney function but uncovers new implications for patterning in response to injury. Understanding how patterning and maturation of the arterial tree affects physiology and response to injury has important implications for enhancing kidney regeneration and tissue engineering strategies.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058775","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