Therefore, to gain insight into the mechanism involved in the AKI-to-CKD transition, we have investigated senescence-related mechanisms, regeneration failure, microvascular rarefaction, and progression to kidney fibrosis in a model of folic acid-induced nephrotoxicity (FAN) in tamoxifen-inducible CCN2 full knockout mice as well as the direct effect of CCN2 on endothelial senescence by in vitro studies in primary cultures of human endothelial cells. The gene discussed is CCN2; the disease is acute kidney injury.