Results
| PMID | 28397725 |
| Gene Name | TGFB1 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Other associated phenotypes |
Endometriosis |
|
Chin Med J (Engl). 2017 Apr 20;130(8):950-956. doi: 10.4103/0366-6999.204112. Yu, Yue-Xin| Xiu, Yin-Ling| Chen, Xi| Li, Ya-Li Department of Obstetrics and Gynecology, Chinese People's Liberation Army General Hospital and Chinese People's Liberation Army Medical School, Beijing 100853; Department of Obstetrics and Gynecology, Chinese People's Liberation Army 202 Hospital, Shen BACKGROUND: Endometriosis (EMs) is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. Transforming growth factor-beta 1 (TGF-beta1) plays a major role in the etiology of EMs. We aimed to determine whether TGF-beta1 affects EMs development and progression and its related mechanisms in hypoxic conditions. METHODS: Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-beta1 or TGF-beta1 inhibitors. The messenger RNA (mRNA) and protein expression levels of TGF-beta1, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1alpha (HIF-1alpha) were measured. A Dual-Luciferase Reporter Assay was used to examine the effect of TGF-beta1 and hypoxia on a VEGF promoter construct. Student's t-test was performed for comparison among groups (one-sided or two-sided) and a value of P < 0.05 was considered statistically significant. RESULTS: TGF-beta1, VEGF, HIF-1alpha mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue (t = 2.16, P = 0.042). EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein (t = 6.84, P = 0.023). VEGF mRNA levels increased 12.5% in response to TGF-beta, whereas the combined treatment of hypoxia/TGF-beta1 resulted in a much higher production (87.5% increases) of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-beta1 (2.6-fold, t = 6.08, P = 0.032) or hypoxia (11.2-fold, t = 32.70, P < 0.001), whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect (18.5-fold, t = 33.50, P < 0.001). CONCLUSIONS: The data support the hypothesis that TGF-beta1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-beta1 and hypoxia is taking place at the transcriptional level. Mesh Terms: Blotting, Western| Cells, Cultured| Endometriosis/genetics/*metabolism| Female| Humans| Hypoxia/genetics/*metabolism| Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism| Transforming Growth Factor beta/genetics/*metabolism| Transforming |
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