Secreted phosphoprotein 1 exacerbates renal ischemia-reperfusion injury by inhibiting PI3K/AKT signaling pathway

Abstract

BackgroundRenal ischemia-reperfusion injury (IRI) is a prevalent reason for acute kidney injury and a key clinical issue for patients under anesthesia and about to have surgery. We aim to investigate the Secreted phosphoprotein 1 (SPP1) role in renal IRI and the underlying mechanisms. MethodsUsing Gene Expression Omnibus (GEO) database helped in analyzing the SPP1 expression in renal IRI. We established two models, a mouse renal ischemia-reperfusion (I/R) besides a hypoxia-reoxygenation (H/R) HK-2 cell. Renal tubular lesions were measured using H&E staining. Depending on the TUNEL assay, immunohistochemistry, qRT-PCR, as well as western blot, we applied the assessment of apoptosis and apoptosis-associated protein levels. At the same time, a western blot was performed for assessing PI3K/AKT pathway-associated proteins. ResultsGEO data and experimental validation revealed elevated SPP1 content in the kidney tissues of renal I/R mice more than in sham mice. In vitro and in vivo studies revealed an increase in cell apoptosis due to SPP1 overexpression, but the opposite is true when SPP1 is silenced. SPP1 downregulation led to high p-PI3K and p-AKT protein levels, and the LY294002 application inhibited SPP1 inhibition-mediated anti-apoptotic effect ConclusionTaken together, SPP1 exacerbates renal IRI in vivo and in vitro via promoting programmed cell death by inhibiting PI3K/AKT signaling pathway.