Molecular Mechanism of G Protein-Coupled Receptor 120 Regulate NLRP3 In-flammasome-Mediated Inflammatory Response in Polycystic Ovary Syndrome
- VernacularTitle:G蛋白偶联受体120调控NLRP3炎症小体参与多囊卵巢综合征炎症反应的分子机制探究
- Author:
Li YANG
1
;
Xiang WU
1
;
Ang LI
1
Author Information
1. 湖南省妇幼保健院妇一科,湖南 长沙 410008
- Publication Type:Journal Article
- Keywords:
G protein-coupled receptor 120;
Nucleotide-binding oligomerization domain-like receptor protein 3;
Polycystic ovary syndrome;
Inflammation
- From:
Journal of Practical Obstetrics and Gynecology
2025;41(3):216-222
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of G protein-coupled receptor 120(GPR120)regulating nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome-mediated inflammatory response in polycystic ovary syndrome(PCOS).Methods:Forty-five wild-type female C57BL/6J mice were randomly divided into three groups:control group,model group,and TUG-891 group,with 15 mice in each group.The model and TUG-891 groups were subcutaneously implanted with 35-day testosterone(T)continuous-release pellets to induce the PCOS model,while control mice received placebo pills.Mice in the TUG-891 group were treated with daily in-traperitoneal injections of TUG-891 starting from day 21 after T implantation.The model group and the control group were injected with the same amount of normal saline intraperitoneally.At the end of the experiment(day 35),the mice were euthanized,and blood and ovarian tissue samples were collected.Immunofluorescence stai-ning was used to detect the expression of GPR120 and NLRP3 proteins in ovarian tissues.Sirius Red staining was performed to detect ovarian fibrosis.Western blot analysis was used to measure the expression of fibrosis factors:α-smooth muscle actin(α-SMA),matrix metalloproteinase 2(MMP2),transforming growth factor-β1(TGF-β1),and inflammatory factors NLRP3,Toll-like receptor 4(TLR4),and tumor necrosis factor-α(TNF-α)in tissues.O-varian granulosa cells(GCs)were isolated from female mice and cultured in DMEM-F12 medium containing 10%fetal bovine serum and 1%penicillin-streptomycin.The cells were divided into the control group,TUG-891 group,T group,and T+TUG-891 group.The vitality and apoptosis of GCs were analyzed using the MTT assay and flow cytometry,respectively.Results:Compared with the model group,the TUG-891 group showed significant increa-ses in body growth,ovarian weight,ovarian index,and the number of pre-ovulatory follicles(P<0.05),as well as significant reductions in sex hormones T,estradiol(E2),luteinizing hormone(LH),and follicle-stimulating hormone(FSH)levels and atretic follicle numbers(P<0.05).Compared with the model group,the Sirius red staining and the relative expressions of α-SMA,MMP2,and TGF-β1 in the ovarian tissue of the TUG-891 group were signifi-cantly lower(P<0.05).Compared with the model group,the expression of GRP120 in the ovarian tissue of the TUG-891 group was significantly increased(P<0.05),and the expression of NLRP3 was significantly decreased(P<0.05).In the in vitro experiments,compared with the T group,the T+TUG-891 group significantly increased the proliferation of GCs(P<0.05),and the apoptosis of GCs and the protein expressions of NLRP3,TLR4 and TNF-α in GCs were significantly decreased(P<0.05).Conclusions:The GPR120 agonist TUG-891 may reduce the chronic low-grade inflammation induced by hyperandrogenism in PCOS mice by inhibiting the production of NLRP3 inflammasome,thereby protecting the growth and development of ovaries and follicles in mice.
