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

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 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 ( ) improved the renal tubular injury, and obviously inhibited the apoptosis and Caspase-3 number in kidney tissues. Besides, decreased proteinuria, and the levels of urea nitrogen and creatinine as well as that of reactive oxygen species induced by ADR. Also, 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.