Effects of circular RNA Ttc3/miR-148a/Rcan2 axis on inflammation and oxidative stress in rats with acute kidney injury induced by sepsis.

UNLABELLED

Aim Increasing evidence demonstrated circular RNAs (circRNAs) are involved in the development of various diseases, including sepsis-induced AKI. Although CIRC-Ttc3 has been proved to regulate cardiac function after myocardial infarction, its role in sepsis-induced AKI remains unclear.

MATERIALS AND METHODS

The AKI rat model was firstly induced by sepsis through cecal ligation puncture (CLP). Serum levels of creatinine, BUN, NGAL, TNF-α, IL-6, SOD, MDA and IL-1β were measured through appropriate kits. The pathological alteration and renal microvascular permeability in renal tissues were determined by HE staining and Evans Blue assays. Cell apoptosis was detected by TUNEL assay. The expression levels of CIRC-Ttc3, miR-148a, TNF-α, IL-1β and iNOS in rats' renal samples were tested by qRT-PCR or/and western blot. The binding ability between CIRC-Ttc3 and miR-148a was evaluated through luciferase reporter, RIP and RNA pull-down assays.

KEY FINDINGS

Kidney injury was found in CLP-treated rats. CIRC-Ttc3 expression was down-regulated, and upregulation of CIRC-Ttc3 improved inflammatory responses and oxidative stress in AKI rats. Mechanismly, CIRC-Ttc3 was confirmed to bind to and negatively regulate miR-148a. Further rescue assays revealed that overexpression of miR-148a rescued the improvement of CIRC-Ttc3 on sepsis-induced AKI. Then, it was illustrated that CIRC-Ttc3 regulated Rcan2 expression by binding to miR-148a. Finally, knockdown of Rcan2 reversed the effects of miR-148a inhibition on sepsis-induced AKI.

SIGNIFICANCE

CIRC-Ttc3 relieved inflammation and oxidative stress through regulating the miR-148a/Rcan2 axis in rats with AKI induced by sepsis. Therefore, CIRC-Ttc3 may be a potential therapeutic target for sepsis-induced AKI.