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.

肾脏缺血再灌注（IR）损伤是泌尿外科手术中的常见问题，并且肾小管（尤其是近端小管）极易受到IR损伤。在这项工作中，我们通过RNA测序检测了正常兔肾脏和IR肾脏之间差异表达的基因（DEG），然后确定基质金属蛋白酶-7（MMP7）在IR损伤的进展中起重要作用。确实，在兔子模型中检测到了肾脏损伤的时间依赖性促进作用，MMP2 / 7/9水平升高和紧密连接蛋白-1（TJP1）降低证明了这一点。此外，在人肾近端肾小管上皮（HK-2）细胞模型中证实了类似的结果。值得注意的是，MMP7的下调通过抑制裂解的MMP2 / 9而不是pro-MMP2 / 9蛋白的表达而影响MMP2 / 9的活性，这直接减轻了HK-2模型中TJP1的降解。相反，MMP7并未受到抑制MMP2 / 9的影响。此外，共免疫沉淀试验表明，敲低的MMP7抑制了MMP2 / 9与TJP1之间的相互作用。总体而言，这项研究表明MMP7可以作为肾小管损伤的早期生物标志物，并揭示MMP7可以通过激活MMP2 / 9降解TJP1破坏肾小管上皮的完整性。