GPR30 Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells via Activating the AKT and ERK Pathways.
AKT and ERK pathways
GPR30
phenotypic switch
varicose veins
vascular smooth muscle cell
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
12
2019
accepted:
14
04
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
23
5
2020
Statut:
epublish
Résumé
Lower extremity varicose veins (LEVVs) are a common venous disorder of venous dilation and tortuosity. The functional integrity of vascular smooth muscle cells (VSMCs), the majority of the cells in venous tissues, and their phenotypic differences play important roles in the occurrence and development of LEVV. However, the underlying mechanism remains unclear. The expression of estrogen receptors ERα and ERβ and G-protein-coupled receptor 30 (GPR30) in LEVV tissues and the role of GPR30 in VSMC phenotypic switching were examined by Western blotting and quantitative real-time PCR. Finally, the related mechanisms underlying LEVVs were explored by Western blotting. The serum estradiol content was increased in LEVV patients compared with normal control patients, but the mRNA levels of ERα and ERβ were not significantly different. GPR30 was overexpressed in LEVVs, and high expression of GPR30 promoted the maintenance of a synthetic phenotype in which OPN, MMP-1 and MMP-9 were highly expressed and α-SMA was poorly expressed in VSMCs. Finally, the mechanism by which GPR30 promotes the phenotypic switching of VSMCs is dependent on the ERK1/2 and AKT pathways. GPR30 may contribute to the pathogenesis of LEVVs by promoting the maintenance of a synthetic phenotype in VSMCs by activating the ERK1/2 and AKT pathways, and GPR30 might be a novel therapeutic target for clinical LEVV treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Lower extremity varicose veins (LEVVs) are a common venous disorder of venous dilation and tortuosity. The functional integrity of vascular smooth muscle cells (VSMCs), the majority of the cells in venous tissues, and their phenotypic differences play important roles in the occurrence and development of LEVV. However, the underlying mechanism remains unclear.
METHODS
METHODS
The expression of estrogen receptors ERα and ERβ and G-protein-coupled receptor 30 (GPR30) in LEVV tissues and the role of GPR30 in VSMC phenotypic switching were examined by Western blotting and quantitative real-time PCR. Finally, the related mechanisms underlying LEVVs were explored by Western blotting.
RESULTS
RESULTS
The serum estradiol content was increased in LEVV patients compared with normal control patients, but the mRNA levels of ERα and ERβ were not significantly different. GPR30 was overexpressed in LEVVs, and high expression of GPR30 promoted the maintenance of a synthetic phenotype in which OPN, MMP-1 and MMP-9 were highly expressed and α-SMA was poorly expressed in VSMCs. Finally, the mechanism by which GPR30 promotes the phenotypic switching of VSMCs is dependent on the ERK1/2 and AKT pathways.
CONCLUSION
CONCLUSIONS
GPR30 may contribute to the pathogenesis of LEVVs by promoting the maintenance of a synthetic phenotype in VSMCs by activating the ERK1/2 and AKT pathways, and GPR30 might be a novel therapeutic target for clinical LEVV treatment.
Identifiants
pubmed: 32440148
doi: 10.2147/OTT.S244128
pii: 244128
pmc: PMC7212987
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3801-3808Informations de copyright
© 2020 Zha et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest in this work.
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