Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF
Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF
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DOI：
10.1530/rep-16-0254
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发表时间：
2016-10-01
期刊：
影响因子：
3.8
通讯作者：
Leung, Peter C. K.
中科院分区：
文献类型：
--
作者：
Chang, Hsun-Ming;Cheng, Jung-Chien;Leung, Peter C. K.
赖氨酰氧化酶 (LOX) 是参与胶原蛋白和弹性蛋白交联的关键酶，对于细胞外基质 (ECM) 的形成至关重要。 LOX介导的ECM重塑在卵泡发育、卵母细胞成熟和黄体形成中发挥着关键作用。迄今为止，LOX在人类卵巢中的调控机制尚未阐明。激活素 A 及其功能受体在早期发育阶段的卵泡中高度表达。它们局部调节卵泡的进展。本研究的目的是研究激活素 A 对从体外受精患者获得的原代和永生化人颗粒叶黄素细胞中 LOX 表达及其胞外酶活性的影响。我们证明，激活素 A 通过激活素/TGF-β I 型受体介导的信号通路显着上调结缔组织生长因子 (CTGF) 和 LOX 的表达。使用靶标缺失小干扰RNA敲低方法，我们进一步证实CTGF表达的上调导致激活素A诱导的LOX表达和活性增加。这些发现可能有助于深入了解卵泡内生长因子调节 LOX 表达以促进人卵巢 ECM 形成和组织重塑的机制。
Lysyl oxidase (LOX) is the key enzyme involved in the crosslinking of collagen and elastin that is essential for the formation of extracellular matrix (ECM). LOX-mediated ECM remodeling plays a critical role in follicle development, oocyte maturation and corpus luteum formation. To date, the regulation of LOX in human ovary has never been elucidated. Activin A and its functional receptors are highly expressed in ovarian follicles from an early developmental stage. They locally regulate follicle progression. The aim of this study was to investigate the effects of activin A on the expression of LOX and its extracellular enzyme activity in primary and immortalized human granulosa-lutein cells obtained from patients undergoing an in vitro fertilization procedure. We demonstrated that activin A significantly upregulated the expression of connective tissue growth factor (CTGF) and LOX via an activin/TGF-beta type I receptor mediated-signaling pathway. Using a target depletion small interfering RNA knockdown approach, we further confirmed that the upregulation of CTGF expression resulted in an activin-A-induced increases in LOX expression and activity. These findings may provide insight into the mechanisms by which intrafollicular growth factors regulate the expression of LOX for ECM formation and tissue remodeling in the human ovary.