Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XISTMicroRNA-124-3pITGB1 Axis in Renal IschemiaReperfusion Injury

Abstract EN

Objective.

Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury.

Total glucosides of paeony (TGP) are a traditional Chinese medicine.

This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action.

Methods.

Rat RI/RI models were constructed by surgical operation.

Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function.

The levels of proinflammatory cytokines were detected by ELISA.

RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro.

The lncRNA XIST (XIST) expression was analyzed by qRT-PCR.

Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay.

Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1.

Results.

TGP improved renal function and inhibited inflammatory responses after RI/RI.

XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression.

Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST.

Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p.

miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells.

Conclusions.

In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats.

In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.