Abstract
The regulation of collagen gene expression by serotonin was investigated in rat uterine smooth muscle cells. Serotonin treatment of myometrial cells caused decreases of up to 10-fold in levels of type I collagen mRNA. Decreases in secreted type 1 collagen protein paralleled decreases in collagen mRNA. The effective half-life of collagen mRNA in serotonin-treated cells was approximately 1.7 days. Selective 5-HT 2 receptor agonists mimicked the effects of serotonin, while the effects of serotonin were blocked by 5-HT 2 antagonists. Nuclear run-on analysis showed that serotonin-dependent decreases in collagen mRNA are accompanied by decreased transcription. Progesterone analogs, which inhibit the serotonin-dependent activation of the gene for interstitial collagenase, had no effect on the ability of serotonin to decrease collagen mRNA. Conversely, the cell-permeable cAMP analog, 8-bromo-cAMP, mimicked the effects of serotonin on type I collagen mRNA and protein. Serotonin also decreased levels of the mRNAs for type III collagen and fibronectin, but had no effect on the mRNAs for type IV collagen. These results indicate that serotonin, previously shown to upregulate the interstitial collagenase gene, downregulates the gene for type I collagen and other extracellular matrix proteins, possibly by a novel mechanism of action downstream of 5-HT 2 receptor binding.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.