Type I collagen, which is mainly composed of collagen type I alpha 1 chain (COL1A1), is the most abundant extracellular matrix (ECM) protein in the mammalian ovary; and the cyclical remodeling of the ECM plays an essential role in the regulation of corpus luteum formation. Our previous studies have demonstrated that TGF‐β1 is a potent inhibitor of luteinization in human granulosa‐lutein (hGL) cells. Whether TGF‐β1 can regulate the expression of COL1A1 during the luteal phase remains to be elucidated. The aim of this study was to investigate the effect of TGF‐β1 on the regulation of COL1A1 expression and the underlying molecular mechanisms using an immortalized hGL cell line (SVOG cells) and primary hGL cells (obtained from 20 consenting patients undergoing IVF treatment). The results showed that TGF‐β1 significantly upregulated the expression of COL1A1. Using inhibition approaches, including pharmacological inhibition (a specific p38 inhibitor, SB203580, and a specific ERK1/2 inhibitor, U0126) and specific siRNA‐mediated knockdown inhibition, we demonstrated that TGF‐β1 promoted the expression and production of COL1A1 in hGL cells, most likely via the ALK5‐mediated p38 signaling pathway. Our findings provide insights into the molecular mechanisms by which TGF‐β1 promotes the deposition of type I collagen during the late follicular phase in humans.

中文翻译：

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p38 信号通路介导 TGF-β1 诱导的人颗粒细胞 I 型胶原沉积增加

I型胶原蛋白，主要由I型胶原蛋白α1链（COL1A1）组成，是哺乳动物卵巢中含量最丰富的细胞外基质（ECM）蛋白；ECM 的周期性重构在调节黄体形成中起重要作用。我们之前的研究表明，TGF-β1 是人颗粒叶黄素 (hGL) 细胞中黄体化的有效抑制剂。TGF-β1 是否可以调节黄体期 COL1A1 的表达仍有待阐明。本研究的目的是使用永生化 hGL 细胞系（SVOG 细胞）和原代 hGL 细胞（从 20 名接受 IVF 治疗的同意患者中获得）研究 TGF-β1 对 COL1A1 表达调节的影响和潜在分子机制。结果表明，TGF-β1 显着上调 COL1A1 的表达。使用抑制方法，包括药理学抑制（一种特定的 p38 抑制剂，SB203580 和一种特定的 ERK1/2 抑制剂，U0126）和特定的 siRNA 介导的敲低抑制，我们证明了 TGF-β1 促进了 hGL 细胞中 COL1A1 的表达和产生，最有可能通过 ALK5 介导的 p38 信号通路。我们的研究结果提供了对 TGF-β1 在人类卵泡晚期促进 I 型胶原沉积的分子机制的见解。我们证明 TGF-β1 促进了 hGL 细胞中 COL1A1 的表达和产生，很可能是通过 ALK5 介导的 p38 信号通路。我们的研究结果提供了对 TGF-β1 在人类卵泡晚期促进 I 型胶原沉积的分子机制的见解。我们证明 TGF-β1 促进了 hGL 细胞中 COL1A1 的表达和产生，很可能是通过 ALK5 介导的 p38 信号通路。我们的研究结果提供了对 TGF-β1 在人类卵泡晚期促进 I 型胶原沉积的分子机制的见解。