title: Growth differentiation factor 8 suppresses cell proliferation by up-regulating CTGF expression in human granulosa cells.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Pan
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China. Electronic address: zhuyim@zju.edu.cn.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada. Electronic address: peter.leung@ubc.ca.
authors.forename: Peter C K
authors.initials: PCK
authors.lastname: Leung
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D055435:Myostatin / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C526317:CCN2 protein, human; C525911:MSTN protein, human; D055435:Myostatin; D051785:Smad Proteins; D055513:Connective Tissue Growth Factor; D029404:Activin Receptors
keywords: CTGF; Cell proliferation; GDF8; Human granulosa cell