title: Peroxisome proliferator-activated receptor-γ agonist inhibits collagen synthesis in human keloid fibroblasts by suppression of early growth response-1 expression through upregulation of miR-543 expression.
abstract: A keloid is a benign skin tumor formed by an overgrowth of granulation tissue in affected patients. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists were reported to be able to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanism of PPAR-γ agonist troglitazone treatment for fibroblasts obtained from keloid patients. The data revealed that troglitazone treatment of keloid fibroblasts (KFs) downregulated the expression of early growth response-1 (Egr1) and collagen-1 (Col1). Level of Egr1 were closely associated with KF-induced fibrosis. The miRNA profiling data revealed that miR-543 was transcriptionally activated after troglitazone treatment. Bioinformatic analysis and experimental data showed that miR-543 was able to target Egr1. ELISA data confirmed that Col1 protein in the supernatant were modulated by the feedback regulatory axis of PPAR-γ agonist-induced miR-543 to inhibit Egr1 expression, whereas PPAR-γ antagonist treatment abolished such effect on Col1 suppression in KFs. This study demonstrated that the PPAR-γ agonist-mediated miR-543 and Egr1 signaling plays an important role in the suppression of collagen synthesis in KFs. Future in vivo studies are needed to confirm these in vitro data.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Hua-Yu
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Urumqi General Hospital of Chinese People's Liberation Army Urumqi, Xinjiang, China.
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Bai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Xie
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, 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 Xi'an, Shaanxi, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Xue-Kang
authors.initials: XK
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Yun-Chuan
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University Xi'an, Shaanxi, 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 Xi'an, Shaanxi, China.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
keywords: Benign tumor; Egr1; PPAR-γ agonist; keloid; miR-543; troglitazone