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Interaction among estrogen, IGF-1, and H2S on smooth muscle cell proliferation
- Source :
- Journal of Endocrinology. 248:17-30
- Publication Year :
- 2021
- Publisher :
- Bioscientifica, 2021.
-
Abstract
- Both estrogen and hydrogen sulfide (H2S) inhibit the proliferation of vascular smooth muscle cells (SMCs) and development of atherosclerosis. In the absence of endogenous H2S as occurred in CSE-knockout (KO) mouse, however, estrogen stimulates the proliferation of vascular SMCs. The underlying mechanisms for this seemingly controversial vascular effect of estrogen are unclear. In the present study, we demonstrated that the stimulatory effect of estrogen on the proliferation of CSE-KO SMCs was suppressed by the inhibitor of insulin-like growth factor-1 receptor (IGF-1R) or knockdown of IGF-1R protein expression. Estrogen downregulated the expression of insulin-like growth factor-1 (IGF-1) and IGF-1R in aortic tissues or aortic SMCs isolated from WT and CSE-KO mice. Furthermore, endogenous H2S downregulated IGF-1R, but upregulated estrogen receptor (ER)-α, in aortic tissues or SMCs. ER-α and IGF-1R were co-located in SMCs and co-immunoprecipitated, which was decreased by H2S. Finally, both endogenous and exogenous H2S induced the S-sulfhydration of IGF-1R, but not ER-α, in WT-SMCs and CSE-KO SMCs, which underlies the decreased formation of IGF-1R/ER-α hybrid in the presence of H2S. Thus, the absence of H2S favors the interaction of estrogen with IGF-1R/ER-α hybrid to stimulate SMCs proliferation. The appreciation of a critical role of H2S in preventing estrogen-induced SMCs proliferation will help better understand the regulation of complex vascular effects of estrogen and sex-related cardiovascular diseases.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Vascular smooth muscle
medicine.drug_class
Endocrinology, Diabetes and Metabolism
Myocytes, Smooth Muscle
Estrogen receptor
030209 endocrinology & metabolism
Endogeny
Receptor, IGF Type 1
03 medical and health sciences
0302 clinical medicine
Endocrinology
Downregulation and upregulation
Internal medicine
medicine
Animals
Hydrogen Sulfide
Protein Phosphatase 2
Insulin-Like Growth Factor I
Receptor
Aorta
Cell Proliferation
Mice, Knockout
Gene knockdown
Estradiol
Cell growth
Chemistry
Estrogen Receptor alpha
030104 developmental biology
Estrogen
cardiovascular system
Female
Subjects
Details
- ISSN :
- 14796805 and 00220795
- Volume :
- 248
- Database :
- OpenAIRE
- Journal :
- Journal of Endocrinology
- Accession number :
- edsair.doi.dedup.....89e5def32120c7127feaf58a60b58979