Mechanism Study Of Radon Regulated Protein-miRNA Network In Skin Tissues

Objective: According to epidemiological studies,there is a certain correlation between Radon exposure and the occurrence of skin-related diseases.However,the effects and mechanisms of Radon on skin tissues have not been reported.The purpose of this study was to study the effects of Radon on skin tissues and cells,and changes in molecular networks.Methods: By establishing a model of mice and skin fibroblasts(WS1)stained with Radon,the effects of Radon on skin tissue and WS1 cells were explored.The differential proteins and mi RNAs in skin tissue were screened,and the biological function of differential proteins on skin cells WS1 was studied through in vitro experiments.(1)Using a multi-functional eco-compartment and a multi-functional ecological cell gas-implantation device to establish a model of radon-infected mice(BALB/c and C57 mice)and a cell staining model.The skin lesions of mice were observed by HE staining,β-galactosidase staining and Masson staining.Through the morphological observation,MTT detection,apoptosis detection,cell cycle detection and nuclear staining of the stained WS1 cells,the changes of the skin cells after staining were observed;(2)The skin tissue proteins of the stained Radon mouse models were collected and passed through isotopes.Labeled relative and absolute quantification(i TRAQ)technology and HPLC/MS techniques were performed on control/stained skin tissue.Bioinformatics analysis was performed on differential proteins through database search;(3)mi RNA microarrays were used to screen differentially expressed mi RNAs in control/ Radon skin tissues.(4)To study the regulation of fatty acid synthase(FASN)expression by mi RNAs;(5)To study the effect of FASN on the biological function of skin cells.Result:(1)Radon can cause skin tissue changes and damage in mice,including thinning and defect of stratum corneum,senescence of skin tissue,and morphological changes of mitochondria in skin tissue;(2)Radon can inhibit the proliferation of skin fibroblasts WS1,increase the rate of cell apoptosis and change the nucleus morphology,resulting in pyknosis and fragmentation;(3)Through proteomic analysis,3,496 differential proteins were screened,of which 45 were upregulated by more than 1.8 times and 83 were downregulated by 0.83.Determined the up-regulated protein that may be involved in the effects of dyeing on mouse skin tissue: fatty acid synthase FASN;(4)Through mi RNA analysis and target gene prediction,57 differential mi RNAs and 5907 downstream target genes were screened out.Down-regulation of mi R206-3p and mi R378a-3p was screened by the Target Scan database;(5)Through the above screening tests,a differential protein interaction network was established after staining,and mi R206-3p and mi R378a-3p was positive correlated with FASN by WB.Overexpression of FASN inhibited the proliferation of skin cells WS1,caused cell cycle S phase block,and also increased apoptotic rate and disrupted nuclear morphology.Conclusion: Radon can cause skin tissue and cell changes or even damage,and affect its biological function;Radon can cause a series of protein and mi RNA changes in the skin;Differentially expressed mi R206-3p and mi R378a-3p have a positive correlation with FASN protein expression.Overexpression of FASN can affect skin cell proliferation and increase cell apoptosis.