Regulation of p53 expression though transforming growth factor β1 (TGFβ1)/Smads pathway in actinic keratosis

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Author:
XU Dan(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
YUAN Rui-hong(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
TU Ying(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
TANG Yang(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
GU Hua(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
ZHANG Li(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
HE Li(Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China)
Journal Title:
Chinese Journal of Dermatology
Issue:
Volume 45, Issue 09, 2012
DOI:
10.3760/cma.j.issn.0412-4030.2012.09.009
Key Word:
Actinic keratosis; Transforming growth factor β1; Smad2 protein; Genes, p53

Abstract: Objective To evaluate the performance of actinic keratosis (AK) tissue as a culture model for the study of interference in transduction pathway,and to explore the mechanism underlying the p53 regulation though TGFβ1/Smads pathway by using the tissue culture model.Methods Twenty-five skin samples from the lesions of patients with AK were cultured,and divided into 5 groups to be treated with TGFβ1 of 10 μg/L for 24 and 48 hours,the tran sforming growth factor (TGF) β1 receptor kinase inhibitor SB431542 of 10 μmol/L for 24 and 48 hours,respectively,or remain untreated.Real time PCR and Western blot were performed to quantify the mRNA expression of p53 and protein expression of p53 and phosphorylated Smad2 in these tissue specimens respectively.Results A significant elevation was observed in the expressions of p53 mRNA ( 13.4968 ± 0.9903 vs.1,P < 0.05) and phosphorylated Smad2 (0.700 ± 0.023 vs.1,P < 0.05) in AK tissues after treatment with TGFβ1 for 24 hours,and in the expressions of p53 mRNA (13.3882 ± 1.6772 vs.1,P < 0.05) and protein (1.009 ± 0.001 vs.0.512 ± 0.005,P < 0.05) after treatment with TGFβ1 for 48 hours,compared with the untreated AK tissues.No significant differences were observed in the expression of p53 protein between the AK tissues treated with TGFβ1 for 24 hours and 48 hours (P > 0.05).SB431542 induced a statistical reduction in the level of phosphorylated Smad2 at 48 hours (0.116 ± 0.003 vs.0.306 ± 0.023,P < 0.05),but no significant changes were observed in the expression of p53 mRNA or protein after SB431542 treatment for 24 or 48 hours.Conclusions AK tissue cultures can serve as a model for the study of interference in signal transduction pathway.TGFβ1 might regulate the expression of p53 protien through Smads pathway in AK.

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