Serotonin regulation of gene expression in uterine extracellular matrix: reciprocal effects on collagens and collagenase

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 mRN...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 1996-07, Vol.120 (2), p.125-132
Main Authors: Passaretti, Teresa V., Wilcox, Brian D., Jeffrey, John J.
Format: Article
Language:English
Subjects:
Animals
cAMP
Cells, Cultured
Collagen - genetics
Collagen - metabolism
Collagenases - genetics
Collagenases - metabolism
Extracellular Matrix Proteins - genetics
Female
Gene Expression Regulation - drug effects
Muscle, Smooth - metabolism
Myometrium
Parturition
Pregnancy
Rat
Rats
Serotonin - pharmacology
Smooth muscle
Uterus
Uterus - metabolism
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Summary: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.
ISSN:0303-7207
1872-8057
DOI:10.1016/0303-7207(96)03827-0