STAT1-p53-p21axis-dependent stress-induced progression of chronic nephrosis in adriamycin-induced mouse model

Abstract

Background: Chronic nephrosis (CN) is an aging-related disease with high mortality. Signal transduction and transcriptional activator 1 (STAT1) protein promotes senescence in human glomerular mesangial cells (HMCs), but whether it affects the progression of adriamycin (ADR)-induced CN in vivo remains unclear. Methods: We established an ADR-induced CN mouse model that was completed in wild-type (wt) mice by a single intravenous injection of 10 mg/kg ADR for 2 or 4 weeks. Clinical indexes in each group were determined. Hematoxylin and eosin staining (H&E) was employed to determine renal histopathological damage, SA-β-gal staining was used to evaluate cell senescence phenotype. TUNEL and immunohistochemistry (IHC) staining were used to detect renal apoptosis. Protein levels of Bcl-2, Bax, STAT1, p53 and p21 were measured by Western Blot. Results: STAT1 intervention ameliorated renal function. H&E staining indicated that STAT1-deficient ( stat1 −/− ) improved the renal tubular injury, and stat1 −/− obviously inhibited the apoptosis and Caspase-3 + number in kidney tissues. Besides, stat1 −/− decreased proteinuria, and the levels of urea nitrogen and creatinine as well as that of reactive oxygen species induced by ADR. Also, stat1 −/− resulted in the reduced expression of p53 and p21. Conclusions: Our current study strongly demonstrated the involvement of the STAT1-p53-p21 axis in the regulation of CN and is a potential target for the nephrosis treatment.