Dimethylnitrosamine(DMN) is an alkylating agent and a known renal carcinogen. A short exposure of renal epithelial cells to cytotoxic concentrations of DMN influences the expression of gap junction proteins. In this study, we examined gap junctional intercellular communication and connexin 43 expression in renal epithelial cells treated with 1% DMN and also examined the effects of dibutyryl-cAMP on preventing gap junctional disturbances. Connexin 43 becomes hypophosphorylated after treatment with 1% DMN for 15 minutes, but this hypophosphorylation is inhibited by pretreatment with dibutyryl-cAMP. These results suggest that changes in gap junction protein expression are early events associated with 1% DMN treatment of renal epithelial cells, and such changes are prevented by dibutyryl-cAMP pretreatment.
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Calcineurin inhibitors (CNIs) are indispensable immunosuppressants for transplant recipients and patients with autoimmune diseases, but chronic use causes nephrotoxicity, including kidney fibrosis. Why inhibiting calcineurin, a serine/threonine phosphatase, causes kidney fibrosis remains unknown. We performed single-nucleus RNA sequencing of the kidney from a chronic CNI nephrotoxicity mouse model and found an increased proportion of injured proximal tubule cells, which exhibited altered expression of genes associated with oxidative phosphorylation, cellular senescence and fibrosis.
View Article and Find Full Text PDFGenetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies. In this study, we investigated zebrafish mutants of , a newly identified ADPKD gene, and observed phenotypes similar to those seen in mammalian models, including kidney cysts and bone defects. Using efficient microhomology-mediated end joining (MMEJ)-based genome editing technology, we demonstrated that CRISPRants recapitulate mutant phenotypes while bypassing the early lethality of the mutants to allow for renal cyst analysis in adult fish.
View Article and Find Full Text PDFRegen Ther
March 2025
Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
Background: Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms.
Methods: A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSC).
Cell Biochem Biophys
January 2025
Department of Zoology, Aligarh Muslim University, Aligarh, UP, India.
The nutritional status of fish is essential for its health, experimental studies, and aquaculture practices. The current study investigated the impact of food deprivation on biochemical parameters, histology of skin, gill, and kidney tissues, and ultrastructure of gills in Clarias batrachus. Fish were subjected to food deprivation for 2, 7, and 15 days resulting in (a) significant increase in plasma cortisol levels, (b) no significant changes in plasma osmolality and plasma glucose content, and (c) significant decrease in liver and muscle glycogen contents.
View Article and Find Full Text PDFClin Exp Nephrol
January 2025
Renal Medicine Division, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, Woodruff Memorial Research Building, Office 338A, Atlanta, GA, 30322, USA.
Background: Renal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF-whether NaCl concentration, independent luminal flow, or the combined total sodium delivery-is still unclear.
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