Abstract: Chen Wenqi *, Bi Zhigang, Dai Jie, Zhang Xiaorong, Xu Huijuan. *Department of Dermatology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China Corresponding author: Xu Huijuan, Email: xuhuij320@163.com 【Abstract】 Objective To evaluate the effect of RNA interference in p53 gene on the expressions of genes involved in ultraviolet B （UVB）-induced premature senescence and photocarcinogenesis in human skin fibroblasts （HSFs）. Methods A previously established HSF cell clone with repressed expression of p53, which was named as HSF-p53, was cultured and irradiated with a subcytotoxic dose （10 mJ/cm2） of UVB once a day for five consecutive days. The HSFs with normal expression of p53 served as the control. Subsequently, β-galactosidase （SA-β-gal）-staining was performed to estimate the degree of senescence, quantitative real-time PCR array was performed to determine the mRNA expressions of photocarcinogenesis- and senescence-associated genes, including p53, p21, p19, p16, pRb, fibronectin, osteonectin, smooth muscle 22 （SM22）, bax, bcl-2, hypoxia-inducible factor-1 α （HIF-1α）, vascular endothelial growth factor（VEGF）, and human double minute-2 （hdm2）. Statistical analysis was carried out by Student′s t test using the software SPSS 10.0. Results The percentage of SA-β-gal-positive cells in irradiated HSF-p53 was 19.70% ± 0.85%, significantly higher than that in unirradiated HSF-p53 （12.77% ± 0.81%, t = 6.45, P ＜ 0.05）, but lower than that in irradiated control HSFs （50.48% ± 5.30%, t = 7.86, P ＜ 0.05）, and similar to that in unirradiated control HSFs （18.50% ± 0.45%, t = 2.57, P > 0.05）. Compared with the control HSFs, the HSF-p53 showed decreased expressions of p21, p19, fibronectin, osteonectin, SM22 and bax genes （all P ＜ 0.05）, but increased expressions of bcl-2, HIF-1α, VEGF and hdm2 genes （all P ＜ 0.05）, and a similar expression of p16 gene （P > 0.05）; the repeated UVB radiation significantly promoted the expressions of p16 and pRb genes （both P ＜ 0.05）, but had no obvious effect on the expressions of the other genes in HSF-p53 compared with unirradiated HSF-p53 （all P > 0.05）. Conclusions The inhibition of p53 expression may decelerate the UVB-induced premature senescence in HSFs, which may be involved in the p53-dependent tumor suppression.

Key words: Genes, p53, RNA interference, Aging, premature, Ultraviolet rays, Fibroblasts