| First Author | Sun H | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 1600 |
| PubMed ID | 35332151 | Mgi Jnum | J:336197 |
| Mgi Id | MGI:7260866 | Doi | 10.1038/s41467-022-29277-6 |
| Citation | Sun H, et al. (2022) Loss of CLDN5 in podocytes deregulates WIF1 to activate WNT signaling and contributes to kidney disease. Nat Commun 13(1):1600 |
| abstractText | Although mature podocytes lack tight junctions, tight junction integral membrane protein claudin-5 (CLDN5) is predominantly expressed on plasma membranes of podocytes under normal conditions. Using podocyte-specific Cldn5 knockout mice, we identify CLDN5 as a crucial regulator of podocyte function and reveal that Cldn5 deletion exacerbates podocyte injury and proteinuria in a diabetic nephropathy mouse model. Mechanistically, CLDN5 deletion reduces ZO1 expression and induces nuclear translocation of ZONAB, followed by transcriptional downregulation of WNT inhibitory factor-1 (WIF1) expression, which leads to activation of WNT signaling pathway. Podocyte-derived WIF1 also plays paracrine roles in tubular epithelial cells, as evidenced by the finding that animals with podocyte-specific deletion of Cldn5 or Wif1 have worse kidney fibrosis after unilateral ureteral obstruction than littermate controls. Systemic delivery of WIF1 suppresses the progression of diabetic nephropathy and ureteral obstruction-induced renal fibrosis. These findings establish a function for podocyte CLDN5 in restricting WNT signaling in kidney. |
