Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys
نویسندگان
چکیده
Aim: Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys currently unknown. We aimed to determine the renal fibrosis and its downstream mechanisms. Methods: Remdesivir active nucleoside metabolite GS-441524 were used treat TGF-? stimulated fibroblasts (NRK-49F) human epithelial (HK2) cells. Vehicle or given by intraperitoneal injection through left ureter unilateral ureteral obstruction (UUO) mice. Serum harvested. concentrations measured using LC-MS/MS. Renal liver function assessed. was evaluated Masson’s trichrome staining Western blotting. Results: inhibited expression fibrotic markers (fibronectin aSMA) NRK-49F HK2 Intraperitoneal attenuated UUO kidneys. unchanged treated Two metabolites detected after injection. Phosphorylation Smad3 that enhanced cell animal models for remdesivir. In addition, Smad7, an anti-fibrotic factor, increased treatment vitro vivo . Moreover, knockdown Smad7 blocked antifibrotic GS RDV Conclusion: inhibits obstructed
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ژورنال
عنوان ژورنال: Frontiers in Pharmacology
سال: 2021
ISSN: ['1663-9812']
DOI: https://doi.org/10.3389/fphar.2021.626510