title: Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist inhibits collagen synthesis in human hypertrophic scar fibroblasts by targeting Smad3 via miR-145.
abstract: The transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) functions to regulate cell differentiation and lipid metabolism. Recently, its agonist has been documented to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanisms and gene interactions in hypertrophic scar fibroblasts (HSFBs) in vitro. HSFBs were cultured and treated with or without PPAR-γ agonist or antagonist for gene expression. Bioinformatical analysis predicted that miR-145 could target Smad3 expression. Luciferase assay was used to confirm such an interaction. The data showed that PPAR-γ agonist troglitazone suppressed expression of Smad3 and Col1 in HSFBs. PPAR-γ agonist induced miR-145 at the gene transcriptional level, which in turn inhibited Smad3 expression and Col1 level in HSFBs. Furthermore, ELISA data showed that Col1 level in HSFBs was controlled by a feedback regulation mechanism involved in PPAR-γ agonist and antagonist-regulated expression of miR-145 and Smad3 in HSFBs. These findings indicate that PPAR-γ-miR-145-Smad3 axis plays a role in regulation of collagen synthesis in HSFBs.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Hua-Yu
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Su
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Xiong-Xiang
authors.initials: XX
authors.lastname: Zhu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Shu-yue
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China. Electronic address: lijunfmmu@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 710032 Xi'an, China. Electronic address: hudahaifmmu@aliyun.com.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
mesh_terms: D000813:Anilides / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002839:Chromans; D024042:Collagen Type I; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D045162:Thiazolidinediones; D003094:Collagen; D000077288:Troglitazone
keywords: Col1; Fibrosis; Hypertrophic scar fibroblasts; PPAR-γ agonist; Smad3; miR-145