CircHIPK3 exacerbates sepsis-induced acute kidney injury and cardiopulmonary function by regulating microRNA-106a-5p/ROCK2 axis

Abstract

ObjectiveThis work was implemented to define the regulatory mechanism of the circularHIPK3 (circHIPK3)/microRNA-106a-5p (miR-106a-5p)/rho-associated kinases 2 (ROCK2) axis in sepsis-induced acute kidney injury (AKI) and cardiopulmonary function. MethodsSepsis mouse models were established by cecal ligation and puncture (CLP). circHIPK3, miR-106a-5p and ROCK2 expression levels in kidney, heart and lung tissues were assessed. The cardiac function, lung wet/dry weight ratio, and Evans blue dye leakage were assessed. Serum markers of myocardial injury, serum markers of kidney injury, as well as serum inflammatory cytokines were assessed. The histopathological changes of heart, lung, and kidney tissues were observed. Moreover, correlations of miR-106a-5p, ROCK2, and circHIPK3 were verified. ResultsIn CLP mice after down-regulating circHIPK3 or up-regulating miR-106a-5p, there were increased LVEF and LVFS and decreased LVESD and LVEDD, serum cTnI and CK-MB levels, lung wet/dry weight ratio, Evans blue dye leakage, serum creatinine, BUN and NGAL levels, serum IL-6, TNF and MCP-1 levels, and reduced heart, lung and liver injury in CLP mice. circHIPK3 bound to miR-106a-5p, and miR-106a-5p downregulated ROCK2 expression. miR-106a-5p inhibition or ROCK2 overexpression reversed the delaying effects of circHIPK3 interference. ConclusioncircHIPK3 aggravates sepsis-induced AKI and cardiopulmonary function via sponging miR-106a-5p and promoting ROCK2 expression.