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.

Association of BTG2, CYR61, ZFP36, and SCD Gene Polymorphisms with Graves' Disease and Ophthalmopathy

“…CYR61 is also overexpressed in RA synovial tissue and plays a critical role in the proliferation of rheumatoid arthritis synovial fibroblasts (30). CYR61 expression is induced in human skin dermal fibroblasts after exposure to cigarette smoke (31). In our study, four SNPs in CYR61 were associated with GO, with one, the promoter SNP rs3753793, even being associated with GD.…”

The CCN family acting throughout the body: recent research developments

“…Clinically, the effect of zoledronate, a drug that represses bone metastasis of tumors, on CCN1 via FOXO 3a is worthy of note in relation to breast cancer chemotherapy (45). The induction of CCN1 in skin fibroblasts by cigarette smoke through Egr1 also suggests a possible role in CCN1 in skin aging due to smoking (46). Other classical CCN2 inducers include angiotensin II and endothelin, the latter of which mediates, in part, the TGF-β-induced enhancement of CCN2 gene expression (3,21,47).…”

Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

“…It was later shown that skin fibroblasts from thyroid healthy individuals express both these genes in response to cigarette smoking [20]. We have recently demonstrated that several immediate early genes including CYR61, EGR1 and COX-2 are overexpressed in orbital tissue of smokers with severe GO as compared to nonsmokers [21].…”