Depleting microRNA-183-3p improves renal tubulointerstitial fibrosis after acute kidney injury via SIRT1/PUMA/FOXO3a deacetylation.

BACKGROUND/AIM:Emerging studies have revealed the mechanism of microRNAs (miRNAs) in acute kidney injury (AKI). However, almost no research focuses on miR-183-3p in AKI. Therefore, this study is started to explore the potential role of miR-183-3p from the perspective of Sirtuin (SIRT1)/forkhead box O3a (FOXO3a)/p53 up-regulated modulator of apoptosis (PUMA) in AKI. METHODS:AKI rat models were established. miR-183-3p, SIRT1, deacetylated FOXO3a and PUMA expression in AKI were detected. The targeting relationship between miR-183-3p and SIRT1 was tested. AKI modeled rats were injected with miR-183-3p- or SIRT1-related sequences to identify their effects on AKI. Rat renal tubular epithelial cells NRK-52E were transfected with miR-183-3p- or SIRT1-related sequences for further exploration of their roles in vitro. RESULTS:Decreased SIRT1 and deacetylated FOXO3a and increased miR-183-3p and PUMA were found in AKI. SIRT1 was targeted by miR-183-3p. Down-regulated miR-183-3p or up-regulated SIRT1 attenuated renal tissue damage and fibrosis, and suppressed renal tubular epithelial cell apoptosis in renal tissues of AKI rats. Down-regulated miR-183-3p or up-regulated SIRT1 promoted proliferation and impaired fibrosis and apoptosis of renal tubular epithelial cells. CONCLUSION:Our study provides evidence that down-regulated miR-183-3p or up-regulated SIRT1 attenuates AKI via PUMA inhibition induced by FOXO3a deacetylation. Thus, miR-183-3p and SIRT1 can be the candidates for therapy of AKI.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}