Renin‐angiotensin blockade ameliorates the progression of glomerular injury in podocyte‐specific Ctcf knockout mice

Aim Several studies have shown that the progression of proteinuria and renal tissue injury is associated with activation of the intrarenal renin‐angiotensin system (RAS). CCCTC‐binding factor (CTCF) is a DNA‐binding factor that plays an essential role in the regulation of gene expression. In the present study, we aimed to investigate the phenotypic effects of CTCF deficiency in podocytes. Methods Angiotensin II type 1 receptor blockers (ARBs) were administered to the podocyte‐specific Ctcf knockout mice, and histological and biochemical analyzes were performed. We also investigated the changes in the expression of podocin in podocyte cell cultures with or without stimulation with angiotensin II from glomeruli isolated using magnetic beads from podocyte‐specific Ctcf knockout mice. Results Mice in which Ctcf was deleted from podocytes developed glomerulopathy and mice developed severe progressive proteinuria, and impaired renal function. Moreover, ARBs suppressed the development of glomerulopathy in podocyte‐specific Ctcf knockout mice. Both real‐time polymerase chain reaction and western blotting showed that podocin expression was decreased in cell cultures stimulated with angiotensin II. Furthermore, RAS components gene expressions in podocyte cell cultures isolated from podocyte‐specific Ctcf knockout mice were significantly increased. Conclusion These results suggest that RAS is involved in the development of glomerulopathy in podocyte‐specific Ctcf knockout mice. Elucidation of the pathophysiology of podocyte‐specific Ctcf knockout mice may provide new insights into the relationship between podocyte injury and chronic glomerulonephritis. Summary at a Glance Renin‐angiotensin system (RAS) is involved in the development of glomerulonephritis in podocyte‐specific Ctcf knock out mice. We suggest that CTCF deletion in podocyte may cause intrarenal RAS activation and podocyte injury.