Defective beta1-integrins expression in arsenical keratosis and arsenic-treated cultured human keratinocytes.
BACKGROUND
beta1-integrins, which localize to the basolateral surface of basal keratinocytes, are important in the differentiation control and proliferation of the epidermis. Many cutaneous diseases with perturbed differentiation, including arsenical keratosis, show altered patterns of integrin distribution and expression. Arsenic may induce arsenical keratosis through the differentiation and apoptosis aberration by integrins. The purpose of this study is to investigate the role of integrin and arsenic in the pathogenesis of arsenical keratosis.


METHODS
Twenty-five specimens obtained from 25 patients with arsenical keratosis disease were studied. Immunohistochemistry staining to beta1, alpha2beta1, or alpha3beta1 integrins was performed in arsenical keratosis and clinically normal perilesional skin. Western blotting was used to assess the expression of integrin beta1 and focal adhesion kinase (FAK) in arsenic-treated cultured keratinocytes.


RESULTS
A decreased expression of beta1, alpha2beta1, or alpha3beta1 integrins was demonstrated in arsenical keratosis and clinical normal perilesional skin in a large proportion of arsenical keratosis cases studied. The expressions of integrin beta1 and FAK were both decreased in arsenic-treated keratinocytes.


CONCLUSIONS
Our results suggest that arsenic induces abnormal differentiation in arsenical keratosis via the effects of integrin expression in keratinocytes.
Lee
Chih-Hung
CH
Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chen
Jau-Shiuh
JS
Sun
Yu-Lan
YL
Liao
Wei-Ting
WT
Zheng
Ya-Wen
YW
Chai
Chih-Zin
CZ
Chen
Gwo-Shing
GS
Yu
Hsin-Su
HS
D000368:Aged; D000369:Aged, 80 and over; D001151:Arsenic / Q000009:adverse effects; D020261:Arsenic Poisoning / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000187:drug effects; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007642:Keratosis / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019012:Integrin beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D001151:Arsenic