Roles of TRPM7 in Renal Ischemia-Reperfusion Injury

: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that is a global health concern associated with high morbidity and mortality. So far, no specific interventions limit injury or improve recovery and survival. Transient receptor potential melastatin 7 (TRPM7), a bifunctional membrane protein, plays key roles in inflammation and cell death. However, the precise role and under-lying mechanism of TRPM7 in IR-induced AKI have not been well defined. Herein, we reviewed the structure and function of TRPM7 as a non-selective ion channel, but Ca2+ and Mg2+-conducting, that mediated the elevation of cytosolic Ca2+ and Mg2+. We then reviewed the mechanism of TRPM7 involved in the pathophysiology of IRI, including inflammatory response, apoptosis and necroptosis, renal microvasculature, as well as maladaptive fibrogenesis leading to chronic kidney disease (CKD). Our previous study has shown that the dynamic change and underlying mechanism of TRPM7 involving in inflammation and apoptosis in in vitro hypoxia/reoxygenation and in vivo renal IRI models. The association between TRPM7, apoptosis and inflammation, as well as related caspase-3, HMGB1 and Bax/Bcl-2 ratio, was also discussed. Disclosing the involvement of TRPM7 in renal IRI might provide new mechanistic insights for a potential biomarker as diagnostic and therapeutic target of AKI.