CNP gene expression is activated by Wnt signaling and correlates withWnt4expression during renal injury
pmid: 12475749
CNP gene expression is activated by Wnt signaling and correlates withWnt4expression during renal injury
C-type natriuretic peptide (CNP) regulates salt excretion, vascular tone, and fibroblast proliferation and activation. CNP inhibits fibroblast activation in vitro and fibrosis in vivo, but endogenous CNP gene ( Nppc) expression during tissue fibrosis has not been reported. We determined that Nppc is induced in renal tubular epithelia and then in interstitial myofibroblasts after unilateral ureteral obstruction (UUO). Induction of Nppcoccurred in identical cell populations to those in which Wnt4 is induced after renal injury. In addition, Nppc was activated in Wnt4-expressing cells during nephrogenesis. Wnt signaling components β-catenin and T cell factor/lymphoid enhancer binding factor (TCF/LEF) specifically bound to cognate elements in the Nppc proximal promoter. Wnt-4, β-catenin, and LEF-1 activated an Nppc transgene in cultured cells, and transgene activation by Wnt-4 and LEF-1 was dependent on the presence of intact cognate elements. These findings suggest that Wnt-4 stimulates Nppc in a TCF/LEF-dependent manner after renal injury and thus may contribute to limiting renal fibrosis.
- University of Mary United States
- Washington University in St. Louis United States
Lymphoid Enhancer-Binding Factor 1, Gene Expression Regulation, Developmental, Natriuretic Peptide, C-Type, Zebrafish Proteins, Kidney, Cell Line, DNA-Binding Proteins, Wnt Proteins, Disease Models, Animal, Mice, Kidney Tubules, Wnt4 Protein, Proto-Oncogene Proteins, Animals, RNA, Messenger, Signal Transduction, Transcription Factors, Ureteral Obstruction
Lymphoid Enhancer-Binding Factor 1, Gene Expression Regulation, Developmental, Natriuretic Peptide, C-Type, Zebrafish Proteins, Kidney, Cell Line, DNA-Binding Proteins, Wnt Proteins, Disease Models, Animal, Mice, Kidney Tubules, Wnt4 Protein, Proto-Oncogene Proteins, Animals, RNA, Messenger, Signal Transduction, Transcription Factors, Ureteral Obstruction
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