Fig. 5.

Scheme depicting the putative role of HCaRG in tubular repair after acute kidney injury (AKI). AKI mainly damages proximal tubular epithelial cells and causes cell death, resulting in necrosis and apoptosis. The induction of cell death is associated with p21 up-regulation dependent on the p53 pathway. Sublethally-injured proximal tubular epithelial cells (PTECs) de-differentiate into mesenchymal cells. De-differentiated cells proliferate and migrate to repair denuded areas. In the repair phase, HCaRG promotes cell migration, and controls PTEC proliferation by acceleration of their re-differentiation via p21 transactivation through the p53-independent pathway, resulting in improved renal function and survival. Lack of HCaRG might lead to uncontrolled cell proliferation and migration of PTECs with de-differentiated phenotypes, resulting in increased risk of chronic kidney diseases and oncogenesis of renal cell carcinoma