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American Journal of Physiology. Renal Physiology

https://read.qxmd.com/read/38482556/mice-with-a-pax2-missense-variant-display-impaired-glomerular-repair
#1
JOURNAL ARTICLE
Joanna Cunanan, Sarada Sriya Rajyam, Bedra Sharif, Khalil Udwan, Akanchaya Rana, Vanessa De Gregorio, Samantha Ricardo, Andrew Elia, Brian Brooks, Astrid Weins, Martin Pollak, Rohan John, Moumita Barua
PAX2 regulates kidney development and its expression persists in parietal epithelial cells (PECs), potentially serving as a podocyte reserve. We hypothesize that mice with a Pax2 pathogenic missense variant ( Pax2 A220G/+ ) have impaired PEC-mediated podocyte regeneration. Embryonic wild type mouse kidneys showed overlapping expression of PAX2/WT-1 until PEC and podocyte differentiation, reflecting a close lineage relationship. Embryonic and adult Pax2 A220G/+ mice have reduced nephron number but demonstrated no glomerular disease under baseline conditions...
March 14, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38482555/tnik-depletion-induces-inflammation-and-apoptosis-ininjured-renal-proximal-tubule-epithelial-cells
#2
JOURNAL ARTICLE
Shayna T J Bradford, Haojia Wu, Yuhei Kirita, Changfeng Chen, Nicole P Malvin, Yasuhiro Yoshimura, Yoshiharu Muto, Benjamin D Humphreys
In the aftermath of acute kidney injury (AKI), surviving proximal tubule epithelia repopulate injured tubules to promote repair. However, a portion of cells fail to repair (termed Failed Repair Proximal Tubule Cells, FR-PTCs) and exert ongoing proinflammatory and profibrotic effects. To better understand the molecular drivers of the FR-PTC state, we reanalyzed a mouse ischemia-reperfusion injury single nucleus RNA-sequencing (snRNA-seq) atlas to identify Traf2 and Nck Interacting Kinase, Tnik, to be exclusively expressed in FR-PTCs, but not in healthy or acutely injured proximal tubules post AKI (2 and 6 weeks) in mice...
March 14, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38482554/predicting-sex-differences-in-the-effects-of-diuretics-in-renal-epithelial-transport-during-angiotensin-ii-induced-hypertension
#3
JOURNAL ARTICLE
Kaixin Zheng, Anita T Layton
Chronic angiotensin II (AngII) infusion is an experimental model that induces hypertension in rodents. The natriuresis, diuresis, and blood pressure responses differ between males and females. This is perhaps not unexpected, given the rodent kidney, which plays a key role in blood pressure regulation, exhibit marked sex differences. Under normotensive conditions, compared to males, the female rat nephron exhibits lower Na+ /H+ exchanger 3 (NHE3) activity along the proximal tubule, but higher Na+ transporter activities along the distal segments...
March 14, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38482553/quantitative-phenotyping-of-nphs1-knockout-mice-as-a-prerequisite-for-gene-replacement-studies
#4
JOURNAL ARTICLE
Florian Buerger, Lea M Merz, Ken Saida, Seyoung Yu, Daanya Salmanullah, Katharina Lemberg, Nils D Mertens, Bshara Mansour, Caroline M Kolvenbach, Kirollos Yousef, Alina Braun, Gijs A C Franken, Nicole Endlich, Ronen Schneider, Shrilee Shril, Friedhelm Hildebrandt
Steroid-resistant nephrotic (SRNS) syndrome is the second most frequent cause of chronic kidney disease before the age of 25 years. Nephrin, encoded by NPHS1, localizes to the slit diaphragm of glomerular podocytes and is the predominant structural component of the glomerular filtration barrier. Biallelic variants in NPHS1 can cause congenital nephrotic syndrome of the Finnish type (CNS-1) for which, to date, no causative therapy is available. Recently, adeno-associated virus (AAV) vectors targeting the glomerular podocyte have been assessed as a means for gene replacement therapy...
March 14, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38450435/mitochondrial-dysfunction-in-the-pathophysiology-of-renal-diseases
#5
REVIEW
Yuxian Guo, Ruochen Che, Peipei Wang, Aihua Zhang
Mitochondria are essential organelles in the human body, serving as the metabolic factory of the whole organism. When mitochondria are dysfunctional, it can affect all organs of the body. The kidney is rich in mitochondria, and its function is closely related to the development of kidney diseases. Studying the relationship between mitochondria and kidney disease progression is of great interest. In the past decade, scientists have made inspiring progress in investigating the role of mitochondria in the pathophysiology of renal diseases...
March 7, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38450434/cognate-antigen-independent-differentiation-of-resident-memory-t-cells-in-chronic-kidney-disease
#6
JOURNAL ARTICLE
Kyle H Moore, Elise N Erman, Amie M Traylor, Stephanie K Esman, Yanlin Jiang, Jennifer R LaFontaine, Anna Zmijewska, Yan Lu, Reham H Soliman, Anupam Agarwal, James F George
Resident memory T cells (TRM s), which are memory T cells that are retained locally within tissues, have recently been described as antigen-specific frontline defenders against pathogens in barrier and non-barrier epithelial tissues. They have also been noted for perpetuating chronic inflammation. The conditions responsible for TRM differentiation are still poorly understood, and their contributions, if any, to sterile models of chronic kidney disease (CKD) remain a mystery. In this study we subjected male C57BL/6J mice and OT-1 transgenic mice to five consecutive days of 2mg/kg Aristolochic acid (AA) injections i...
March 7, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38450433/the-degree-of-aortic-occlusion-in-the-setting-of-trauma-alters-the-extent-of-acute-kidney-injury-associated-with-mitochondrial-preservation
#7
JOURNAL ARTICLE
Biebele Abel, John Mares, Justin Hutzler, Babita Parajuli, Lalitha Kurada, Joseph M White, Brandon W Propper, Ian J Stewart, David M Burmeister
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control non-compressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severe trauma patients. Herein, we investigated how the degree of aortic occlusion alters AKI in a porcine model. Female Yorkshire-cross swine (n=16, 68.1±0.7Kg) were anesthetized, and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring...
March 7, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38420675/liver-and-spleen-predominantly-mediate-calciprotein-particle-clearance-in-a-rat-model-of-chronic-kidney-disease
#8
JOURNAL ARTICLE
Lara W Zeper, Caro Bos, Pieter A Leermakers, Gerben M Franssen, René Raavé, Joost G J Hoenderop, Jeroen H F de Baaij
Calciprotein particles (CPP) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in the circulation. However, in chronic kidney disease (CKD), the phosphate load exceeds the mineral buffering capacity, resulting in the formation of crystalline CPP2 particles. CPP2 have been associated with cardiovascular events and mortality. Moreover, CPP2 have been demonstrated to induce calcification in vitro. In this study, we examined the fate of CPP2 in a rat model of CKD...
February 29, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38420674/podocytes-from-hypertensive-and-obese-mice-acquire-an-inflammatory-senescent-and-aged-phenotype
#9
JOURNAL ARTICLE
Sierra R McKinzie, Natalya Kaverina, Robert Allen Schweickart, Christopher Chaney, Diana G Eng, Beatriz Maria Veloso Pereira, Bryan Kestenbaum, Jeffrey W Pippin, Oliver Wessely, Stuart J Shankland
Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA-sequencing of isolated podocytes from experimental models and their respective controls...
February 29, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38385175/-in-chronic-kidney-disease-altered-cardiac-metabolism-precedes-cardiac-hypertrophy
#10
JOURNAL ARTICLE
Matthew J Williams, Carmen M Halabi, Hiral M Patel, Zachary Joseph, Kyle McCommis, Carla Weinheimer, Attila Kovacs, Florence Lima, Brian Finck, Hartmut Malluche, Keith A Hruska
Conduit arterial disease in CKD is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to human stage 4-5 CKD. PTH and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased and VSMC transdifferentiation was absent...
February 22, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38385174/sex-differences-in-sympathetic-activity-and-vascular-stiffness-in-adults-with-chronic-kidney-disease-ckd
#11
JOURNAL ARTICLE
Matias G Zanuzzi, Jinhee Jeong, Dana R DaCosta, Jeanie Park
BACKGROUND: Chronic kidney disease (CKD) is characterized by sympathetic nervous system (SNS) overactivity that contributes to increased vascular stiffness and cardiovascular risk. While it is well established that SNS activity and vascular stiffness are substantially elevated in CKD, whether sex differences in autonomic and vascular function exist in CKD remains unknown. We tested the hypothesis that compared to females, males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness...
February 22, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38385173/human-soluble-prorenin-receptor-expressed-in-mouse-renal-collecting-duct-show-sex-specific-effect-on-cardiorenal-function
#12
JOURNAL ARTICLE
Gertrude Arthur, Audrey Poupeau, Katherine Biel, Jeffrey L Osborn, Ming Gong, Terry D Hinds, Volkhard Lindner, Analia S Loria
Soluble prorenin receptor (sPRR), a component of the renin angiotensin system (RAS), has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. Despite studies showing that sPRR in kidney is produced by renal collecting duct (CD) tubular cells, its biological actions modulating cardiorenal function remains unknown. Therefore, this study aimed to create a new murine model to investigate how expressing human sPRR (HsPRR) in CD influence the intrarenal RAS status and renal hemodynamics in male and female mice fed a regular chow...
February 22, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38357719/distinct-developmental-reprogramming-footprint-of-macrophagesduring-acute-kidney-injury-across-species
#13
JOURNAL ARTICLE
Michal Mrug, Elias Mrug, Frida Rosenblum, Jiandong Chen, Xiangqin Cui, Anupam Agarwal, Abolfazl Zarjou
Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. Development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and increase in health care expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to treatment of AKI continues to principally encompass supportive measures...
February 15, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38299216/-strategies-to-mitigate-acute-kidney-injury-risk-during-physical-work-in-hot-environments
#14
REVIEW
Abdulaziz Masoud, Zachary J McKenna, Zidong Li, Michael R Deyhle, Christine M Mermier, Zachary J Schlader, Fabiano T Amorim
Prolonged physical work in the heat can reduce renal function and increase the risk of acute kidney injury (AKI). This is concerning given that the latest climate change projections forecast a rise in global temperature as well as the frequency, intensity, and duration of heatwaves. This means that outdoor and indoor workers in the agriculture or construction industries will be exposed to higher heat stress in the years ahead. Several studies indicate a higher incidence of chronic kidney disease from nontraditional origins (CKDnt) in individuals exposed to high temperatures, intense physical work, and/or recurrent dehydration...
February 1, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38299215/rodent-models-of-aki-and-aki-ckd-transition-an-update-in-2024
#15
REVIEW
Ying Fu, Yu Xiang, Qingqing Wei, Daria Ilatovskaya, Zheng Dong
Despite known drawbacks, rodent models are essential tools in the research of renal development, physiology, and pathogenesis. In the past decade, rodent models have been developed and used to mimic different etiologies of acute kidney injury (AKI), AKI to chronic kidney disease (CKD) transition or progression, and AKI with comorbidities. These models have been applied for both mechanistic research and preclinical drug development. However, current rodent models have their limitations, especially since they often do not fully recapitulate the pathophysiology of AKI in human patients, and thus need further refinement...
February 1, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38299214/c-terminal-fragment-of-fibroblast-growth-factor-fgf-23-improves-heart-function-in-murine-models-of-high-intact-fgf23
#16
JOURNAL ARTICLE
Ming Chang Hu, James A Reneau, Mingjun Shi, Masaya Takahashi, Gaozhi Chen, Moosa Mohammadi, Orson W Moe
Cardiovascular disease (CVD) is the major cause of death in chronic kidney disease (CKD) and is associated with high circulating fibroblast growth factor (FGF)-23 levels. It is unresolved whether high circulating FGF-23 is a mere biomarker or pathogenically contributes to cardiomyopathy. It is also unknown whether the C-terminal FGF23 peptide (cFGF23), a natural FGF23 antagonist proteolyzed from intact FGF23 (iFGF23), retards CKD progression and improves cardiomyopathy. We addressed these questions in three murine models with high endogenous FGF23 and cardiomyopathy...
February 1, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38299213/activation-of-farnesoid-x-receptor-retards-expansion-of-renal-collecting-duct-cells-derived-cysts-via-inhibition-of-cftr-mediated-cl-secretion
#17
JOURNAL ARTICLE
Nipitpon Srimai, Kanlayanee Tonum, Sunhapas Soodvilai
The transcription factor farnesoid X receptor (FXR) regulates energy metabolism. Specifically, FXR functions to regulate CFTR-mediated Cl- secretion in intestinal epithelial cells. Therefore, this study aimed to investigate the role of FXR in CFTR-mediated Cl- secretion in renal tubular cells, and to further elucidate its effects on renal cyst formation and growth. CFTR-mediated Cl- transport was evaluated via short-circuit current ( I SC ) measurements in MDCK cell monolayers and primary rat inner medullary collecting duct (IMCD) cells...
February 1, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38269409/ks-wnk1-is-required-for-the-renal-response-to-extreme-changes-in-potassium-intake
#18
JOURNAL ARTICLE
Jessica Paola Bahena-Lopez, Laura Vergara, Valeria De la Peña, Miguel A Gutiérrez-Gallardo, Paulina López-Ibargüen, Janeth Alejandra García, Héctor Carbajal-Contreras, Norma Vázquez, Ruth Rincón-Heredia, Felipe Masso, Norma A Bobadilla, María Castañeda-Bueno, David H Ellison, Gerardo Gamba, María Chávez-Canales
KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+ -Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low potassium diet...
January 25, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38269408/mitochondria-derived-reactive-oxygen-species-contribute-to-synergistic-interaction-of-diabetes-and-hypertension-in-causing-chronic-kidney-injury
#19
JOURNAL ARTICLE
Zhen Wang, Yiling Fu, Alexandre A da Silva, Jussara M do Carmo, Alan Mouton, Ana Carolina M Omoto, Xuan Li, Jaylan Sears, John E Hall
Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. The combination of DM and HTN significantly accelerates development of renal injury; however, the underlying mechanisms of this synergy are still poorly understood. This study assessed whether mitochondria (MT) dysfunction is essential in developing renal injury in a rat model with combined DM and HTN. Type 1 DM was induced in Wistar rats by streptozotocin (STZ)...
January 25, 2024: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/38269407/the-apical-70-ps-potassium-k-channel-in-the-thick-ascending-limb-of-henle-s-loop-is-a-large-conductance-na-and-cl-activated-k-na-1-1-like-channel
#20
JOURNAL ARTICLE
Elise de Combiens, Nadia Frachon, Lydie Cheval, Stéphane Lourdel, Marc Paulais
Apical potassium channels are crucial for thick ascending limb (TAL) of Henle's loop transport function. The ROMK ( KNCJ1 ) gene encodes a 30-pS K channel whose loss of function causes the reduced NaCl reabsorption in the TAL associated with Type 2 Bartter's syndrome. In contrast, the molecular basis of a functionally ROMK-related 70-pS K channel is still unclear. The aim of this study was to highlight new specific channel properties that may give insights on its molecular identity. Using the patch-clamp technique on the apical membrane of mouse split-open TAL tubules, we observed that 70-pS K channel activity, but not ROMK channel activity, increases with the internal Na+ and Cl- concentrations, with relative 50 % effective concentrations ( EC50 ) and Hill coefficients ( nH ) of 40...
January 25, 2024: American Journal of Physiology. Renal Physiology
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