title: The role of ERK and JNK signaling in connective tissue growth factor induced extracellular matrix protein production and scar formation.
abstract: CCN2 plays an important role in the pathogenesis of hypertrophic scars (HTSs). Although CCN2 is involved in many fibroproliferative events, the CCN2 induction signaling pathway in HTSs is yet to be elucidated. Here, we first investigated the effect of the mitogen-activated protein kinases (MAPKs) on CCN2-induced α-smooth muscle actin (α-SMA) and collagen I expression in human HTS fibroblasts (HTSFs). Then, we established HTSs in a rabbit ear model and determined the effect of MAPKs on the pathogenesis of HTSs. MAPK pathways were activated by CCN2 in HTSFs. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors significantly inhibited CCN2-induced expression of α-SMA and collagen I in HTSFs. In the rabbit ear model of the HTS, JNK and ERK inhibitors significantly improved the architecture of the rabbit ear scar and reduced scar formation on the rabbit ear. Our results indicate that ERK and JNK mediate collagen I expression and scarring of the rabbit ear, and may be considered for specific drug therapy targets for HTSs.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, Shaanxi, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Hu
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fang
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.forename: Yaojun
authors.initials: Y
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jihong
authors.initials: J
authors.lastname: Shi
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Ji
authors.forename: Weixia
authors.initials: W
authors.lastname: Cai
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Bai
authors.forename: Xiongxiang
authors.initials: X
authors.lastname: Zhu
authors.forename: Juntao
authors.initials: J
authors.lastname: Han
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C526317:CCN2 protein, human; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases