ZONAB regulates renal cyst formation in nphp1 knockout mice

Tubular dilation and cyst formation at the corticomedullary junction are distinct pathological features of nephronophthisis (NPH) and may be associated with disease progression. However, the mechanism of renal cyst formation in NPH is unclear. Increased cell proliferation is necessary for cyst formation. ZONAB, a tight junction-associated transcriptional regulatory factor, targets proliferative factors, such as CCND1 and PCNA. In this study, we explored the role of ZONAB in renal cyst formation and its possible mechanism in nphp1 knockout (nphp1^KO) mice. We found that the expression of ZONAB, CCND1, and PCNA was increased in the kidney tissue of the nphp1^KO mice but was mainly confined to renal cyst cells. ZONAB knockdown inhibited renal cyst formation and tubular dilatation and decreased the expression of CCND1 and PCNA in the nphp1^KO mice. We concluded that ZONAB plays an important role in renal cyst formation in the NPH, possibly through the regulation of CCND1 and PCNA.