title: Neuregulin induces CTGF expression in hypertrophic scarring fibroblasts.
abstract: Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. These pathogenic mechanisms are regulated by connective tissue growth factor (CTGF) and transforming growth factor-β. We found that neuregulin-1 (NRG1), as well as NRG receptors, HER-2, and HER-3 were upregulated in HTS fibroblasts (HTSF), compared with normal fibroblasts. Furthermore, NRG1 stimulation increased the expression of CTGF in HTSF. In the presence of inhibitors of PI3K, Src, Smad, or reactive oxygen species, the effect of NRG1 on CTGF expression decreased significantly. In particular, the combination of LY294002 or PP2 with SB431542 blocked NRG1-mediated CTGF expression in HTSF. Finally, we demonstrated that siRNA for CTGF, AG825, LY294002, and PP2, either alone or in co-treatment, effectively reduced extracellular matrix expression. Taken together, our results suggest that NRG1 is involved in fibrotic scar pathogenesis via PI3K- or Src-mediated CTGF expression.
authors.affiliation: Specialization Research Center, Hallym University Burn Institute, Hangang Sacred Heart Hospital, Hallym University, Seoul, South Korea.
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Kim
authors.forename: Ihn-Geun
authors.initials: IG
authors.lastname: Choi
authors.forename: Boung-Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Je Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Cheong Hoon
authors.initials: CH
authors.lastname: Seo
mesh_terms: D002056:Burns / Q000473:pathology; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000473:pathology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; C094131:NRG1 protein, human; D020890:Neuregulin-1; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases