Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells
Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells
复制标题
转化生长因子-β 1 通过下调人颗粒叶黄素细胞中的 MIR29A 来增加赖氨酰氧化酶的表达
DOI：
10.1530/rep-16-0144
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发表时间：
2016-09-01
期刊：
影响因子：
3.8
通讯作者：
Yang, Xiaokui
中科院分区：
文献类型：
--
作者：
Fang, Ying;Chang, Hsun-Ming;Yang, Xiaokui
赖氨酰氧化酶（LOX）是细胞外基质形成和稳定的关键酶，在颗粒细胞中表达，在调节颗粒细胞分化、卵母细胞成熟和排卵中起关键作用。迄今为止，LOX在人类颗粒细胞中的表达调控仍然是未知的。在这项研究中，使用原代和永生化的人颗粒黄体细胞，我们证明了转化生长因子（TGF）-β 1（TGFB 1）通过TGF-β I型受体介导的信号通路上调LOX表达和下调microRNA-29 a（MIR 29 A）表达。此外，我们发现MIR 29 A在两种类型的细胞中下调LOX的表达。此外，MIR 29 A的下调有助于TGFB 1诱导的LOX表达增加，因为MIR 29 A抑制剂抑制MIR 29 A不仅逆转了MIR 29 A诱导的LOX下调，而且增强了TGFB 1诱导的LOX上调。我们的研究结果表明，TGFB 1和MIR 29 A可能在调节排卵期细胞外基质重塑中发挥重要作用。
Lysyl oxidase (LOX), a key enzyme in the formation and stabilization of the extracellular matrix, is expressed in granulosa cells and plays a critical role in the regulation of granulosa cell differentiation, oocyte maturation and ovulation. To date, the regulation of LOX expression in human granulosa cells remains largely unknown. In this study, using primary and immortalized human granulosa lutein cells, we demonstrated that transforming growth factor (TGF)-beta 1 (TGFB1) upregulated LOX expression and downregulated microRNA-29a (MIR29A) expression via a TGF-beta type I receptor-mediated signaling pathway. Additionally, we showed that MIR29A downregulated the expression of LOX in both types of cells. Furthermore, the downregulation of MIR29A contributed to the TGFB1-induced increase in LOX expression because the inhibition of MIR29A with a MIR29A inhibitor not only reversed the MIR29A-induced downregulation of LOX but also enhanced the TGFB1-induced upregulation of LOX. Our findings suggest that TGFB1 and MIR29A may play essential roles in the regulation of extracellular matrix remodeling during the periovulatory phase.