Sfrp1 遺伝子は急性腎不全において腎線維化の進行を制御している

Renal fibrosis is responsible for progressive renal diseases that cause chronic renal failure. Secreted Frizzled-related protein 1 (Sfrp1) is highly expressed in kidney, although little is known about connection between the protein and renal diseases. Here we focused on Sfrp1 to investigate its roles in renal fibrosis using a mouse model of unilateral ureteral obstruction (UUO). In wild-type mice, the expression of Sfrp1 protein was markedly increased after UUO. The kidneys from Sfrp1 knockout mice showed significant increase in expression of myofibrobast markers, alpha-smooth muscle actin (SMA). Sfrp1 deficiency also increased protein levels of the fibroblast genes, Vimentin, and decreased those of the epithelial genes, E-cadherin, indicated that enhanced epithelial-to-mesenchymal transition (EMT). There was no difference in the levels of canonical Wnt signaling; rather the levels of phosphorylated c-Jun and JNK were more increased in the Sfrp1-/- obstructed kidney. Moreover, the apoptotic cell population was significantly elevated in the obstructed kidneys from Sfrp1-/- mice following UUO, but was slightly increased in those from wild-type mice. These results indicate that Sfrp1 is required for inhibition of renal damage through non-canonical Wnt/PCP pathway.

特別講演要旨 (Summary of Special Lecture)