title: Cigarette smoke-induced early growth response-1 regulates the expression of the cysteine-rich 61 in human skin dermal fibroblasts.
abstract: Tobacco smoke is known to be an element contributing to accelerate premature skin ageing. Cysteine-rich 61 (Cyr61) is a member of the connective tissue factor CCN (Cyr61, CTGF and Nov) family, and early growth response-1 (Egr-1) is a generally expressed member of the zinc-finger family of transcription factors. To investigate the regulatory potential of Egr-1 on expression of Cyr61 by smoking, this study examined the hypothesis that cigarette smoke-induced Egr-1 induces expression of Cyr61 in human skin dermal fibroblasts (HSDF). HSDF were exposed to different concentrations of cigarette smoke extract (CSE) for 24 h; a cytotoxicity assay was then performed for the detection of cell proliferation. Results of Western blot and reverse transcription-polymerase chain reaction (RT-PCR) showed that CSE induces a transient synthesis of Egr-1 in HSDF. Cyr61 mRNA and protein levels showed a marked increase in a time-dependent manner after CSE exposure. Following transfection with an Egr-1 overexpression vector, HSDF showed increased activity of the Cyr61 promoter in a dose-dependent manner. Using Egr-1 interfering RNA, we confirmed that CSE-induced Cyr61 expression was dependent on Egr-1 expression. Findings of this study indicate that Egr-1-dependent induction of Cyr61 may contribute to premature skin ageing by smoking.
authors: Laboratory of Cell Signaling and Nanomedicine, Division of Brain Korea 21 Project for Biomedical Science and Department of Dermatology, Korea University College of Medicine, Seoul, Korea.
authors: Ji Na
authors: JN
authors: Kim
authors: Hee Joo
authors: HJ
authors: Kim
authors: Sang Hoon
authors: SH
authors: Jeong
authors: Young Chul
authors: YC
authors: Kye
authors: Sang Wook
authors: SW
authors: Son
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012867:Skin / Q000166:cytology; D012906:Smoke / Q000009:adverse effects*; D015854:Up-Regulation / Q000235:genetics; D014026:Nicotiana
chemical_list: C501848:CCN1 protein, human; D024042:Collagen Type I; D055515:Cysteine-Rich Protein 61; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; D012906:Smoke; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1