Secreted Frizzled-related protein 1 (Sfrp1) regulates the progression of renal fibrosis in a mouse model of obstructive nephropathy.

Abstract

Renal fibrosis is responsible for progressive renal diseases that cause chronic renal failure. Sfrp1 (secreted Frizzled-related protein 1) 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 knock-out mice showed significant increase in expression of myofibrobast markers, α-smooth muscle actin (αSMA). 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. 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 the non-canonical Wnt/PCP pathway.

• Authors: Makoto Matsuyama, Akane Nomori, Kyomi Nakakuni, Akihiko Shimono, Masaki Fukushima
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 45 Pg. 31526-33 (Nov 07 2014) ISSN: 1083-351X [Electronic] United States
• PMID: 25253698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• CTNNB1 protein, mouse
• Cadherins
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• Recombinant Proteins
• Sfrp1 protein, mouse
• Wnt Proteins
• beta Catenin

Topics

• Animals
• Cadherins (metabolism)
• Disease Models, Animal
• Disease Progression
• Epithelial-Mesenchymal Transition
• Fibroblasts (metabolism)
• Fibrosis (metabolism)
• Gene Deletion
• HEK293 Cells
• Humans
• Intercellular Signaling Peptides and Proteins (physiology)
• Kidney (metabolism, pathology)
• Kidney Diseases (metabolism)
• Membrane Proteins (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Recombinant Proteins (metabolism)
• Signal Transduction
• Ureteral Obstruction (genetics, pathology)
• Wnt Proteins (metabolism)
• beta Catenin (metabolism)