Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3KAkt Signaling Pathway In Vitro

الملخص EN

Background.

Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited.

This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms.

Methods.

Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway).

Cell viability was evaluated with a CCK-8 assay.

Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method.

Apoptosis was detected with Annexin V staining.

Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins.

Results.

Ioversol reduced the viability of HK-2 cells.

Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol.

The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased.

As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol.

These effects were reversed when HK-2 cells were cotreated with RLX.

However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked.

Conclusion.

Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.