MMP7 damages the integrity of the renal tubule epithelium by activating MMP2/9 during ischemia-reperfusion injury.

Abstract

Renal ischemia-reperfusion (IR) injury is a common issue in urological surgery, and the renal tubules, particularly the proximal tubules, are extremely vulnerable to IR injury. In this work, we detected the differently expressed genes (DEGs) between normal rabbit kidneys and IR kidneys by RNA-sequencing, then identified that matrix metalloproteinase-7 (MMP7) played an important role in the progress of IR injury. Indeed, A time-dependent promotion of renal injury was detected in rabbit model, as demonstrated by the increased levels of MMP2/7/9, and the decreased of tight junction protein-1 (TJP1). Furtherly, similar results were confirmed in human renal proximal tubule epithelial (HK-2) cells model. Notably, downregulation of MMP7 affected the activity of MMP2/9 by suppressing expression of cleaved-MMP2/9 not the pro-MMP2/9 protein, which directly alleviated the degradation of TJP1 in HK-2 model. On the contrary, MMP7 had not been affected by inhibiting MMP2/9. In addition, coimmunoprecipitation assay showed that knockdown MMP7 restrained the interaction between MMP2/9 and TJP1. Collectively, this study suggested that MMP7 could serve as early biomarkers for renal tubular injury, and revealed that MMP7 could destroy the integrity of tubular epithelium through degrading TJP1 by activating MMP2/9.