Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of chloracne patients exposed to dioxins

Abstract

a b s t r a c tObjective: Chloracne 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. Methods: Epidermal 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. Results: p-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. Conclusions:The 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.

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

“…The reduced number of sebaceous glands and sebocytes may be associated with the altered metabolism of the mature sterol-binding protein (mSREBP-1), resulting from AMP-activated protein kinase (AMPK) activation [155]. On the other hand, the MAPK signaling pathway is also crucial for skin lesion formation in chloracne patients, as AhR activation in chloracne induces the activation of EGFR and MAPK [156]. EGFR and AhR compete for common coactivator p300 for their transcriptional activity.…”

Chloracne and Hyperpigmentation Caused by Exposure to Hazardous Aryl Hydrocarbon Receptor Ligands

“…In addition to the acceleration of keratinization, an immunohistological study revealed an activation of EGFR in chloracne [79]. AMP-activated protein kinase (AMPK) is activated by AHR and downregulates protein turnover of the mature sterol regulatory element-binding protein (mSREBP-1), leading to a decrease in the size of sebaceous glands and the number of sebocytes within each gland in the skin [80].…”

Sodium 3,5,6-trichloropyridin-2-ol poisoning

“…Also, individuals with chloracne had abnormal levels of keratin 17 in the epidermis and abnormal levels of glutamine enzyme gene and protein. These findings suggested that normal proliferation and differentiation of cells were altered and led to the development of chloracne (Liu et al, 2011).…”