title: Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells.
abstract: 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)-β1 (TGFB1) upregulated LOX expression and downregulated microRNA-29a (MIR29A) expression via a TGF-β 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.
authors.affiliation: Department of Human Reproductive MedicineBeijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China Department of Obstetrics and GynaecologyChild & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and GynaecologyChild & 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 & 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 & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Klausen
authors.affiliation: Department of Obstetrics and GynaecologyChild & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada peter.leung@ubc.ca xiaokuiyang2012@163.com.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
authors.affiliation: Department of Human Reproductive MedicineBeijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China peter.leung@ubc.ca xiaokuiyang2012@163.com.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Yang
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D008249:Protein-Lysine 6-Oxidase