title: CCN2 and CCN5 exerts opposing effect on fibroblast proliferation and transdifferentiation induced by TGF-β.
abstract: Epidural fibrosis might occur after lumbar discectomy and contributes to failed back syndrome. Transforming growth factor (TGF)-β has been reported to influence multiple organ fibrosis, in which connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 2 (CCN2) and CCN5 are involved. However, the effect of CCN2 and CCN5 on TGF-β induced fibrosis has not yet been elucidated. This study reports that CCN2 and CCN5 play opposing roles in cell proliferation and transdifferentiation of human skin fibroblasts or rabbit epidural scar-derived fibroblasts exposed to TGF-β. We observed that TGF-β1 induced fibroblasts proliferation and differentiation in a dose-dependent manner (from 0 μg/L to 20 μg/L). Meanwhile, CCN2 expression is up-regulated while CCN5 expression is inhibited by TGF-β1 exposure. Furthermore, it is demonstrated that CCN2 overexpression leads to promoted proliferation and elevated collagen and α-smooth muscle actin (α-SMA) expression, which are inhibited by CCN5 overexpression. Moreover, it is shown that the cysteine knot (CT) domain, present in CCN2 but absent in CCN5, plays an essential part in fibroblast proliferation and differentiation. Additionally, enhanced TGF-β and CCN2 expression but decreased CCN5 expression is found in rabbit epidural scar-derived fibroblasts. Overall, the results show the opposing effects of CCN2 and CCN5 on fibroblast proliferation and transdifferentiation induced by TGF-β.
authors.affiliation: Department of Orthopaedics, Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Xi'an, Shaanxi, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Xu
authors.affiliation: Xi 'an Medical College, Xi'an, Shaanxi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Xi 'an Medical College, Xi'an, Shaanxi, China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Liu
authors.affiliation: Xi 'an Medical College, Xi'an, Shaanxi, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Xi'an, Shaanxi, China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of the Faculty of Public Health, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Xi'an, Shaanxi, China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004824:Epidural Space / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C526317:CCN2 protein, human; C413323:CCN5 protein, human; D012097:Repressor Proteins; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor
keywords: CCN2; CCN5; epidural scar; fibroblasts; proliferation; transdifferentiation