Chloroform induces cystein-rich 61, a mediator of collagen homeostasis via early growth response-1 dependent pathway in human skin dermal fibroblasts

Abstract

Volatile organic compounds (VOCs) are major air pollutants known to have adverse effects on skin. Many reports have shown an association between air pollutants and skin aging. However, there is no report on VOCs association with skin aging. The aim of this study is to identify the biologic effects of VOCs on fibroblasts. We investigated the effects of chloroform on cysteine-rich 61 (CYR61) expression in human skin fibroblasts using western blot and reverse transcription-polymerase chain reaction. We also observed the change of type I procollagen and matrix metalloproteinase after exposure to chloroform using western blot. We explored the involvement of early growth response-1 (Egr-1) using siRNAs in the fibroblasts. Chloroform exposure increased the expression of CYR61 protein and mRNA level. Elevated CYR61 downregulates type I procollagen and upregulates MMP-1. Egr-1 overexpression upregulates CYR61 promoter activity. CYR61 promoter activity was lower in Egr-1 siRNA-transfected fibroblasts. The present study demonstrates that CYR61 is transcriptionally regulated by chloroform exposure through transcription factor Egr-1, and alters collagen homeostasis in human skin fibroblasts.