关键词: 3D in vitro model SABV TGF-β1 TGF-β3 cornea corneal fibrosis corneal stroma sex hormone receptors

Mesh : Humans Female Male Corneal Stroma Transforming Growth Factor beta3 Estrogen Receptor alpha Receptors, Kisspeptin-1 Estrogen Receptor beta / genetics Transforming Growth Factor beta1 / genetics Transforming Growth Factor beta Follicle Stimulating Hormone

来  源:   DOI:10.3390/ijms241713635   PDF(Pubmed)

Abstract:
This study investigated the interplay between transforming growth factor beta (TGF-β1/T1 and TGF-β3/T3), and sex hormone receptors using our 3D in vitro cornea stroma model. Primary human corneal fibroblasts (HCFs) from healthy donors were plated in transwells at 106 cells/well and cultured for four weeks. HCFs were supplemented with stable vitamin C (VitC) and stimulated with T1 or T3. 3D construct proteins were analyzed for the androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα) and beta (ERβ), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), gonadotropin-releasing hormone receptor (GnRHR), KiSS1-derived peptide receptor (KiSS1R/GPR54), and follicle-stimulating hormone subunit beta (FSH-B). In female constructs, T1 significantly upregulated AR, PR, ERα, FSHR, GnRHR, and KiSS1R. In male constructs, T1 significantly downregulated FSHR and FSH-B and significantly upregulated ERα, ERβ, and GnRHR. T3 caused significant upregulation in expressions PR, ERα, ERβ, LHR, FSHR, and GNRHR in female constructs, and significant downregulation of AR, ERα, and FSHR in male constructs. Semi-quantitative Western blot findings present the interplay between sex hormone receptors and TGF-β isoforms in the corneal stroma, which is influenced by sex as a biological variable (SABV). Additional studies are warranted to fully delineate their interactions and signaling mechanisms.
摘要:
这项研究调查了转化生长因子β(TGF-β1/T1和TGF-β3/T3)之间的相互作用,和性激素受体使用我们的3D体外角膜基质模型。将来自健康供体的原代人角膜成纤维细胞(HCF)以106个细胞/孔铺板在transwell中并培养4周。HCFs补充有稳定的维生素C(VitC)并用T1或T3刺激。分析3D构建体蛋白的雄激素受体(AR),孕激素受体(PR),雌激素受体α(ERα)和β(ERβ),黄体生成素受体(LHR),卵泡刺激素受体(FSHR),促性腺激素释放激素受体(GnRHR),KiSS1衍生肽受体(KiSS1R/GPR54),和卵泡刺激素亚基β(FSH-B)。在女性结构中,T1显著上调AR,PR,ERα,FSHR,GnRHR,KiSS1R在男性结构中,T1显著下调FSHR和FSH-B,显著上调ERα,ERβ,和GnRHR。T3引起表达PR的显著上调,ERα,ERβ,LHR,FSHR,和GNRHR在女性结构中,和AR的显著下调,ERα,和FSHR在男性结构中。半定量Westernblot发现显示性激素受体和TGF-β同工型在角膜基质中的相互作用,受性别作为生物变量(SABV)的影响。有必要进行其他研究以充分描述它们的相互作用和信号传导机制。
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