Effects and Mechanism of lncRNA CRNDE on Sepsis-Induced Acute Kidney Injury

Abstract EN

Objective.

To investigate the effects of lncRNA CRNDE on sepsis-associated acute kidney injury in the human kidney 2 cell line and explore the potential mechanisms.

Methods.

HK-2 cells were treated with lipopolysaccharides to induce injuries.

The expression of CRNDE and miR-146a in HK-2 cells were altered by a transient transfection assay.

Cell apoptosis was detected by a flow cytometry assay, and the levels of inflammatory cytokines including TNF-α, IL-6, IL-8, and IL-1β were assessed by ELISA.

Furthermore, western blot analysis was performed to detect the expression levels of TLR4/NF-κB pathway-related proteins.

And a luciferase reporter gene assay was used to verify if miR-146a was the target of CRNDE.

Results.

LPS treatment increased CRNDE expression in HK-2 cells.

CRNDE overexpression enhanced cell injuries in HK-2 cells significantly increasing inflammatory cytokine levels, including TNF-α, IL-6, IL-8, and IL-1β, and cell apoptosis.

In addition, CRNDE overexpression further activated the TLR4/NF-κB pathways in HK-2 cells.

Inversely, opposite results were observed in the miR-146a mimic treatment group, and the miR-146a inhibitor could reverse the protein expression changes of TLR4/NF-κB in the si-CRNDE and LPS treatment group.

Conclusion.

This study demonstrated that CRNDE overexpression could activate the TLR4/NF-κB signaling pathway by regulating miR-146a, which accelerated LPS-induced inflammation and apoptosis in HK-2 cells.