title: Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF.
abstract: 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-β 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.
authors.affiliation: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada Obstetrics and Gynecology Hospital of Fudan UniversityShanghai, China.
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Klausen
authors.affiliation: Obstetrics and Gynecology Hospital of Fudan UniversityShanghai, China.
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and GynaecologyChild and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada peter.leung@ubc.ca.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
mesh_terms: D028341:Activins / Q000494:pharmacology*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000201:enzymology*; D006080:Ovarian Follicle / Q000187:drug effects / Q000201:enzymology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D055513:Connective Tissue Growth Factor; D008249:Protein-Lysine 6-Oxidase