title: Cigarette smoke-induced Egr-1 represses T beta R-II expression in human skin dermal fibroblasts.
abstract: Tobacco smoking is one of the many factors that contribute to premature skin aging, but the exact mechanism by which smoking induces facial wrinkling is still poorly understood. To investigate the regulatory potential of early growth response-1 (Egr-1) on the premature skin aging by smoking, this study examined the hypothesis that cigarette smoke-induced Egr-1 represses T beta R-II expression in human skin dermal fibroblasts (HSDFs). The protein and mRNA expressions of Egr-1 and T beta R-II were detected using Western blot and real-time RTPCR in HSDFs after exposure to cigarette smoke extract (CSE). Egr-1 and T beta R-II promoter activities were analyzed in CSE-exposed fibroblasts using luciferase assay. T beta R-II promoter activity was also evaluated in HSDFs to be transfected with Egr-1 overexpression vector. To investigative Egr-1-specific effects, we utilized Egr-1 small interfering RNA (siRNA) to inhibit Egr-1 expression. The expressions of Egr-1 protein and mRNA were increased in a time and dose-dependent manner. CSE also induced Egr-1 at the transcription level. Egr-1 was induced though phosphorylation of Erk1/2 after CSE exposure in HSDFs. We also observed the immunostained Egr-1 proteins were mainly localized from the cytoplasm to the nucleus after CSE treatment by immunocytochemical analyzes. Furthermore, T beta R-II protein and mRNA levels were decreased in a dose-dependent manner by CSE and T beta R-II promoter activity was significantly repressed by CSE. HSDFs transfected with Egr-1 overexpression vector showed significantly reduced T beta R-II promoter activity. In addition, T beta R-II mRNA levels were upregulated in HSDFs transfected with Egr-1 siRNA, suggesting that T beta R-II expressional downregulation by CSE is induced via an Egr-1-dependent mechanism. This study suggests that the downregulation of T beta R-II expression by cigarette smoke-induced Egr-1 may contribute to smoking-induced premature skin aging.
authors.affiliation: Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Ji Na
authors.initials: JN
authors.lastname: Kim
authors.forename: Jeung Tae
authors.initials: JT
authors.lastname: Jeong
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Jeong
authors.forename: Sun Ae
authors.initials: SA
authors.lastname: Kim
authors.forename: Kyung Goo
authors.initials: KG
authors.lastname: Lee
authors.forename: Jae Bin
authors.initials: JB
authors.lastname: Shin
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kye
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism*; D052816:Foreskin / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II