title: Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-β1/Smad signaling pathway.
abstract: Dermal fibrosis is characterized by collagen accumulation and hyperproliferation of fibroblasts. NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat (NLRs) family, has recently been implicated in the development of hepatic fibrosis. However, the role of NLRC5 in dermal fibrosis remains unknown. Therefore, herein, we investigated the effects of NLRC5 on keloid fibroblasts (KFs) and transforming growth factor-β1 (TGF-β1)-induced collagen expression and explored the underlying mechanism. We observed that NLRC5 mRNA and protein levels were highly expressed in KFs, silencing NLRC5 greatly suppressed TGF-β1-induced KFs proliferation. Silencing NLRC5 also obviously inhibited the expression of type I collagen, CTGF and α-smooth muscle actin (α-SMA) in human KFs induced by TGF-β1, as well as the expression of TGF-β receptor I and II. Furthermore, silencing NLRC5 suppressed the expression of TGF-β1-induced Smad2 and Smad3 phosphorylation in human KFs. Taken together, our study suggest that silencing NLRC5 reduced ECM expression in KFs through inhibiting the TGF-β1/Smad signaling pathway. Therefore, NLRC5 may represent a promising target for treatment of the keloid disease.
authors.affiliation: Shandong Clinical College of Skin Diseases, Anhui Medical University, Jinan 250000, China; Department of Dermatology, Yantaishan Hospital, Yantai 264001, China.
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Yantaishan Hospital, Yantai 264001, China.
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
authors.forename: Guan-Zhi
authors.initials: GZ
authors.lastname: Chen
authors.affiliation: Basic Medicine Faculty of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: ronghuixa@163.com.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Fang
authors.affiliation: Shandong Clinical College of Skin Diseases, Anhui Medical University, Jinan 250000, China; Shandong Provincial Institute of Dermatology and Venereology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250000, China; Shandong Provincial Hospital for Skin Diseases, Jinan 250021, China; Shandong Provincial Medical Center for Dermatovenereology, Jinan 250021, China; Shandong Provincial Key Lab for Dermatovenereology, Jinan 250021, China. Electronic address: furenzhangskin@163.com.
authors.forename: Fu-Ren
authors.initials: FR
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007627:Keloid / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051899:Smad2 Protein; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D047908:Intracellular Signaling Peptides and Proteins; C548042:NLRC5 protein, human; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1
keywords: Keloid fibroblasts (KFs); NLRC5; TGF-β1/Smad signaling; Transforming growth factor-β1 (TGF-β1)