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Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of chloracne patients exposed to dioxins |
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| Authors: | Liu Jing Zhang Chun-mei Coenraads Pieter-Jan Ji Zhi-ying Chen Xi Dong Li Ma Xiao-ming Han Wei Tang Nai-jun |
| Affiliation: | a Department of Occupational Health, School of Public Health, Tianjin Medical University, 22# Qixiangtai Road, Tianjin 300070, China b Institute of Occupational Disease Control and Prevention, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China c Dermatology Department, University Medical Centre Groningen, University of Groningen, The Netherlands d Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, USA e Shanxi Osteorad Biomaterial Co., Ltd., China Institute for Radiation Protection, Shanxi 030006, China f Dahua Hospital, Tanggu District, Tianjin 300450, China |
| Abstract: | ObjectiveChloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of chloracne related to dioxin exposures.MethodsEpidermal tissues of twelve chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively.Resultsp-EGFR and p-MAPK were found in all chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all chloracne lesions, but none in controls (P = 0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum.ConclusionsThe results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of chloracne related to dioxin exposures. |
| Keywords: | EGFR, epidermal growth factor receptor MAPK, mitogen-activated protein kinase CK17, cytokeratin 17 TGk, transglutaminase 1 TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin AhR, aromatic hydrocarbon receptor ARNT, aryl hydrocarbon nuclear translocator AP-1, activator protein-1 PTK, protein tyrosine kinase |
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