Fibroblast growth factor receptor 2 promotes the proliferation, migration, and invasion of ectopic stromal cells via activation of extracellular-signal-regulated kinase signaling pathway in endometriosis

Xu, Yuan; Gao, Feng; Zhang, Jingyong; Cai, Pingping; Xu, Dongsheng

doi:10.1080/21655979.2022.2054207

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…These bacteria were also positively correlated to proinflammatory markers IL-1α ( p < 0.05, p < 0.05, p < 0.01, respectively) and IL-1β ( p < 0.05, p < 0.01, p < 0.01, respectively). Additionally, these bacteria were positively correlated to fibroblast growth factor 2 and FGF-2 ( p < 0.05, p < 0.01, p < 0.01, respectively), which has been associated with proliferation, migration, and invasion of ectopic stromal cells [ 62 ]. M. lornae and B. vaginale C were also positively correlated with IL-12 p70 ( p < 0.05, p < 0.05, respectively) and fractalkine ( p < 0.05, p < 0.05, respectively).…”

Section: Resultsmentioning

confidence: 99%

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain

Jimenez,

Norton,

Diadala

et al. 2024

BMC Med

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Background Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient’s quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP. Methods Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2. Results Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺. Conclusions Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

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Section: Resultsmentioning

confidence: 99%

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain

Jimenez,

Norton,

Diadala

et al. 2024

BMC Med

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“…Activation of the ERK signaling pathway is able to promote the proliferation of tumor cells and enhance the processes of tumor cell migration and invasion (65)(66)(67)(68), all of which leads to an acceleration of tumor progression. PD98059 could exert a positive protective effect, as it can inhibit tumor cell proliferation, migration and invasion (66,(69)(70)(71). In addition, activation of the ERK pathway has been demonstrated to mediate cell apoptosis, and this effect can be blocked by PD98059 (61)(62)(63).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 promotes β‑amyloid peptide degradation through inhibition of the ERK/PPARγ phosphorylation pathway in an Alzheimer's disease neuronal model

Quan,

Ma,

et al. 2023

Exp Ther Med

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β-Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin-degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator-activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE , and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ 1-42 , ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra- and extracellular Aβ 1-42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co-expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ 1-42 treatment, reduce the levels of intra- and extraneuronal Aβ 1-42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co-expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.

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“…The FGFR2 gene encodes a protein that is a member of the fibroblast growth factor receptor (FGFR) family [ 27 ]. FGFR2 was shown to be involved in biological processes such as cell proliferation, migration, tube formation and anti-inflammation in previous studies [ 28 , 29 ]. Our data revealed that overexpression of FGFR2 restored hRMECs function under HG and miR-524-5p overexpression conditions.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of lncRNA TUG1 alleviates diabetic retinal vascular dysfunction through regulating miR-524-5p/FGFR2

et al. 2022

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Long noncoding RNAs (LncRNAs) have been shown to play critical roles in the development of diabetic retinopathy (DR), which is often regarded as the most frequent cause of visual loss in the world. This study investigated the effect and mechanism of lncRNA taurine-upregulated gene 1 (TUG1) in DR. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that TUG1 was upregulated in streptozotocin (STZ)-induced rat model of DR and human retinal microvascular endothelial cells (hRMECs) incubated with high glucose (HG). TUG1 suppression decreased the proliferation, migration, and angiogenesis of HG-induced hRMECs. TUG1 sponges miR-524-5p, which is downregulated in hyperglycemia. Additionally, the fibroblast growth factor receptor 2 (FGFR2) was verified as a miR-524-5p target gene and was overexpressed in HG-treated hRMECs. More notably, overexpression of FGFR2 has been shown to significantly reduce the impact of miR-524-5p overexpression. Additionally, TUG1 silencing ameliorates diabetes mellitus-induced retinal vascular impairment in vivo. Taken together, suppressing TUG1 impairs vascular function in diabetic retinas via controlling miR-524-5p and FGFR2, suggesting a possible therapy method for DR.

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Fibroblast growth factor receptor 2 promotes the proliferation, migration, and invasion of ectopic stromal cells via activation of extracellular-signal-regulated kinase signaling pathway in endometriosis

Cited by 8 publications

References 43 publications

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain

Ginsenoside Rg1 promotes β‑amyloid peptide degradation through inhibition of the ERK/PPARγ phosphorylation pathway in an Alzheimer's disease neuronal model

Knockdown of lncRNA TUG1 alleviates diabetic retinal vascular dysfunction through regulating miR-524-5p/FGFR2

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