Objective: To investigate the effects of interferon-gamma (IFN-gamma) on tubular epithelial-myofibroblast transdifferentiation (TEMT) induced by transforming growth factor (TGF-beta1).
Methods: The normal rat kidney tubular epithelial cells (NRK52E) were cultured and divided into blank (NRK52E cells only) control group, TGF-beta1 (3 ng/mL) treated group, IFN-gamma (1000 IU/mL) treated group, and IFN-gamma inhibition group (TGF-beta1 3 ng/mL + IFN-gamma 200, 400, 600, 1000, 2000, 3000 IU/mL). After 72 hours of treatment, the morphology of cells was observed under phase-contrast microscopy and scanning electron microscopy. The expressions of a-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were detected by immunocytochemistry. Flowcytometry was employed to measure the percentage of alpha-SMA+ cells and the mean channel fluorescence (MCF). The expressions of alpha-SMA mRNA and CTGF mRNA were examined by reverse transcription-polymerase chain reaction analyses (RT-PCR). The level of collagen in the culture supernatant was measured by Enzyme-linked immunoadsordent assay (ELISA).
Results: NRK52E cells cultured in the control group showed a classic cobblestone morphology. TGF-beta1 induced NRK52E cells to transdifferentiate into myofibroblast-like cells, which showed strong alpha-SMA immunostaining. The TGF-beta1 treated cells had higher percentage of a-SMA+ cells, MCF and alpha-SMA mRNA, increased CTGF mRNA expression, and ascended collagen III than the blank controls (P<0.05). IFN-gamma treated alone did not make any changes to the cell morphology, the expressions of alpha-SMA mRNA and CTGF mRNA and the level of collagen III (P>0.05). IFN-gamma exerted a strong inhibitory effect on the TEMT induced by TGF-beta1. With the increase of IFN-gamma, the percentage of alpha-SMA+ cells, the level of collagen III, and the expressions of alpha-SMA mRNA and CTGF mRNA decreased (P<0.05).
Conclusion: IFN-gamma inhibits the TEMT induced by TGF-beta1 and reduces the level of collagen III.
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Inflamm Res
January 2025
Department of Nephrology, the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: The pathogenesis of acute kidney injury (AKI) is not fully understood. Tax1-binding protein 1 (TAX1BP1) modulates inflammation and apoptosis through the NF-kB signaling pathway, however, its specific role in ischemic AKI remains unclear.
Methods: We injected a TAX1BP1 overexpression plasmid into the tail vein of male C57BL/6 mice, followed by clamping the bilateral renal arteries to induce AKI.
Front Pharmacol
December 2024
Department of Urology, The First Affiliated hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Background: The calcium-sensitive receptor (CaSR) has been identified as a key factor in the formation of kidney stones. A substantial body of research has illuminated the function of CaSR in stone formation with respect to oxidative stress, epithelial injury, crystal adhesion, and stone-associated proteins. Nevertheless, as a pivotal molecule in renal calcium excretion, its pathway that contributes to stone formation by regulating calcium supersaturation remains underexplored.
View Article and Find Full Text PDFRen Fail
December 2024
Department of Nephrology, Nantong Hospital to Nanjing University of Chinese Medicine, Nantong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China.
Objective: This study was recruited to investigate the role of mitophagy in activating NLRP3 inflammasome in the kidney of uric acid (UA) nephropathy (UAN) rats.
Methods: This study developed a uric acid nephropathy (UAN) rat model divided into five groups: Negative control (NC), UAN model (M), UAN + autophagy inhibitor (3-MA), UAN + lysosome inhibitor (CQ), and ROS scavenger (N-acetylcysteine, N). H&E staining assessed renal structure, ROS levels were measured with 2, 7dichlorofluorescin diacetate, and ELISA measured serum markers (, , cystatin , , , ).
J Physiol Pharmacol
October 2024
Department of Clinical Laboratory, Yantaishan Hospital, Yantai City, Shandong Province, 264003, China.
Melatonin (Mel) has been documented to modulate epithelial-mesenchymal transition (EMT) in cellular systems. The interstitial transformation of renal tubular epithelial cells constitutes a key pathogenic mechanism underlying renal fibrosis. This study aims to elucidate the role of Mel in the EMT process of renal tubular epithelial cells.
View Article and Find Full Text PDFDrug Dev Ind Pharm
December 2024
Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P. R. China.
Objectives: Sepsis-associated acute kidney injury (SA-AKI) is a significant clinical challenge with high morbidity and mortality. Low bioavailability of protopanaxadiol (PPD) limits its clinical application. In this study, PPD was encapsulated with chitooligosaccharide (COS) modified polylactic-co-glycolic acid (PLGA) to develop novel nanomedicines for the treatment of SA-AKI.
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