Cigarette smoke-induced Egr-1 represses TβR-II expression in human skin dermal fibroblasts

Ji Na Kim, Jeung Tae Jeong, Sang Hoon Jeong, Sun Ae Kim, Kyung Goo Lee, Jae Bin Shin, Young Chul Kye, Sang Wook Son

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 TβR-II expression in human skin dermal fibroblasts (HSDFs). The protein and mRNA expressions of Egr-1 and TβR-II were detected using Western blot and real-time RTPCR in HSDFs after exposure to cigarette smoke extract (CSE). Egr-1 and TβR-II promoter activities were analyzed in CSE-exposed fibroblasts using luciferase assay. TβR-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, TβR-II protein and mRNA levels were decreased in a dose-dependent manner by CSE and TβR-II promoter activity was significantly repressed by CSE. HSDFs transfected with Egr-1 overexpression vector showed significantly reduced TβR-II promoter activity. In addition, TβR-II mRNA levels were upregulated in HSDFs transfected with Egr-1 siRNA, suggesting that TβR-II expressional downregulation by CSE is induced via an Egr-1-dependent mechanism. This study suggests that the downregulation of TβR-II expression by cigarette smoke-induced Egr-1 may contribute to smoking-induced premature skin aging.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalToxicology
Volume275
Issue number1-3
DOIs
Publication statusPublished - 2010 Sep 1

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Keywords

  • Cigarette smoking
  • Egr-1
  • Human skin fibroblasts
  • Skin aging
  • Type II TGF-β receptor

ASJC Scopus subject areas

  • Toxicology

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