Upregulation of miR-126 inhibits podocyte injury in sepsis via EGFL6/DKC1 signaling pathway

Abstract

Sepsis-induced cardiorenal syndrome is one of the multiple organ dysfunctions observed in sepsis. It is determined by a primary dysfunction in one organ that leads to secondary injury to another organ. Studies have shown the involvement of microRNAs (miRs) in the diagnosis and prognosis of several pathologies. However, the implication of miR-126 in the podocyte damage associated with sepsis has not been evaluated until now. In the current study, the miR-126 expression was downregulated in a podocyte injury model together with downregulation of nephrin expression. The transfection of podocytes from podocyte injury group with miR-126 mimics demonstrated an increase in cell proliferation and a decrease in cell apoptosis. Bioinformatics analysis predicted that the target of miR-126 was epidermal growth factor-like domain multiple 6 (EGFL6) and dyskeratosis congenita 1 (DKC1) and these were confirmed by dual-luciferase reporter assay. miR-126 upregulation determined EGFL6 and DKC1 upregulation and prevented podocyte injury. The current study demonstrated that overexpression of miR-126 could protect podocytes from sepsis-induced injury through an EGFL6/DKC1 signaling pathway.