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C-type natriuretic peptide induces human colonic myofibroblast relaxation
Taned Chitapanarux1, Stephen L Chen, Helen Lee
1Department of Medicine, CURE Digestive Diseases Research, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
American Journal of Physiology. Gastrointestinal and Liver Physiology
|September 6, 2003
Summary
C-type natriuretic peptide (CNP) rapidly relaxes intestinal subepithelial myofibroblasts (SEM) by reducing myosin light chain phosphorylation. This suggests CNP may play a role in intestinal wound healing.
Area of Science:
- Gastroenterology
- Cell Biology
- Molecular Biology
Background:
- Intestinal injury response relies on subepithelial myofibroblast (SEM) tension regulation.
- Signals inducing intestinal SEM relaxation remain largely uncharacterized.
Purpose of the Study:
- To investigate if C-type natriuretic peptide (CNP) induces intestinal SEM relaxation.
- To elucidate the molecular mechanisms underlying CNP-mediated SEM relaxation.
Main Methods:
- Cultured human colonic SEM were treated with CNP.
- Isometric tension, intracellular cGMP, myosin regulatory light chain (MLC) phosphorylation, and cytosolic Ca2+ were measured.
- Effects of calyculin-A on CNP-induced changes were assessed.
Main Results:
- CNP induced rapid and sustained SEM relaxation (up to 2 hours).
- CNP increased intracellular cGMP and decreased MLC phosphorylation in a dose-dependent manner.
- CNP also caused a transient increase in cytosolic Ca2+; calyculin-A blocked CNP's effect on MLC phosphorylation.
Conclusions:
- CNP induces intestinal SEM relaxation via cGMP-dependent reduction of MLC phosphorylation.
- CNP signaling pathways are crucial for regulating intestinal myofibroblast tension.
- CNP may be a therapeutic target for promoting intestinal wound healing.