title: Knockdown of IRF3 inhibits extracellular matrix expression in keloid fibroblasts.
abstract: Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism. Our results indicated that the expression of IRF3 was highly expressed in human keloid tissues. Down-regulation of IRF3 significantly inhibited KF proliferation and the expression of type I collagen and α-smooth muscle actin (α-SMA), as well as suppressed the expression of TGF-β receptor I and II in TGF-β1-stimulated KFs. Furthermore, down-regulation of IRF3 suppressed the phosphorylation levels of Smad2 and Smad3 in human KFs induced by TGF-β1. Taken together, our data showed that down-regulation of IRF3 inhibited the proliferation and ECM expression in KFs via suppressing the TGF-β1/Smad signaling pathway. Thus, our findings suggest that IRF3 may represent a promising target for treatment of the keloid disease.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of WenZhou Medical University, WenZhou 325000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of WenZhou Medical University, WenZhou 325000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of WenZhou Medical University, WenZhou 325000, China. Electronic address: lin_xihua@163.com.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Lin
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of WenZhou Medical University, WenZhou 325000, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Li
authors.affiliation: Department of Hepatic Surgery, The First Affiliated Hospital of WenZhou Medical University, WenZhou 325000, China.
authors.forename: Qi-Yu
authors.initials: QY
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007627:Keloid / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D050838:Interferon Regulatory Factor-3; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: Extracellular matrix (ECM); Interferon regulatory factor 3 (IRF3); Keloid fibroblasts (KFs); TGF-β1/Smad pathway