Chang Hsun-Ming, Pan Hui-Hui, Cheng Jung-Chien, Zhu Yi-Min, Leung Peter C K
Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.
Mol Cell Endocrinol. 2016 Feb 15;422:9-17. doi: 10.1016/j.mce.2015.11.009. Epub 2015 Nov 11.
Connective tissue growth factor (CTGF) is a matricellular protein that plays a critical role in the development of ovarian follicles. Growth differentiation factor 8 (GDF8) is mainly, but not exclusively, expressed in the mammalian musculoskeletal system and is a potent negative regulator of skeletal muscle growth. The aim of this study was to investigate the effects of GDF8 and CTGF on the regulation of cell proliferation in human granulosa cells and to examine its underlying molecular determinants. Using dual inhibition approaches (inhibitors and small interfering RNAs), we have demonstrated that GDF8 induces the up-regulation of CTGF expression through the activin receptor-like kinase (ALK)4/5-mediated SMAD2/3-dependent signaling pathways. In addition, the increase in CTGF expression contributes to the GDF8-induced suppressive effect on granulosa cell proliferation. Our findings suggest that GDF8 and CTGF may play critical roles in the regulation of proliferative events in human granulosa cells.
结缔组织生长因子（CTGF）是一种基质细胞蛋白，在卵巢卵泡发育中起关键作用。生长分化因子8（GDF8）主要但并非仅在哺乳动物的肌肉骨骼系统中表达，是骨骼肌生长的有效负调节因子。本研究的目的是探讨GDF8和CTGF对人颗粒细胞增殖调控的影响，并研究其潜在的分子决定因素。使用双重抑制方法（抑制剂和小干扰RNA），我们证明GDF8通过激活素受体样激酶（ALK）4/5介导的SMAD2/3依赖性信号通路诱导CTGF表达上调。此外，CTGF表达的增加有助于GDF8对颗粒细胞增殖的抑制作用。我们的研究结果表明，GDF8和CTGF可能在人颗粒细胞增殖事件的调控中起关键作用。
