MiR-378a-5p-targeted silencing of FAIM promotes pro-inflammatory factor release from psoriatic subcutaneous adipocytes
Objective To investigate the expression of miR-378a-5p in subcutaneous adipose tissue of psoriasis and its impact on the pathogenesis of psoriasis.Methods A psoriasis mouse model was constructed from SPF grade 4～6 week old female C57BL/6 mice,where the model group was psoriasis mice and the control group was C57BL/6 mice with petroleum jelly cream.Hematoxylin eosin(HE)staining was used to observe the pathological changes in skin tissue.Real time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the mRNA levels of miR-378a-5p and Fas apoptosis inhibitory molecule(FAIM)in subcutaneous adipose tissue,and Western blot(WB)was used to detect the protein level of FAIM.Adipocytes were isolated for subsequent experiments.Dual-luciferase reporter assay,qPCR,and WB were used to validate the targeting relationship between miR-378a-5p and FAIM.Plasmids for overexpression and knockdown of miR-378a-5p,as well as FAIM knockdown,were constructed.After transfection into adipocytes,enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of inflammatory factors--tumor necrosis factor α(TNF-α),interleukin-1(IL-1),and interleukin-6(IL-6)in culture me-dium.Results The skin tissue of the model group mice showed obvious pathological morphology of psoriasis.In the adipose tissue of psoriasis mouse model,the mRNA level of miR-378a-5p was upregulated,while the mRNA and protein levels of FAIM were downregulated,and the dif-ferences were statistically significant(P<0.05).Dual-luciferase reporter assay,qPCR,and WB confirmed that FAIM was a downstream target of miR-378a-5p.Compared to the NC mimics group,the miR-378a-5p mimics group showed a significant increase in the release of inflamma-tory factors TNF-α,IL-1,and IL-6 from adipocytes(P<0.05).Compared to the NC inhibitors group,the miR-378a-5p inhibitors group showed a significant decrease in the release of TNF-α,IL-1,and IL-6(P<0.05).Compared to the control group,the FAIM inhibitors group showed a significant increase in the release of TNF-α,IL-1,and IL-6 from adipocytes,which could be reversed by miR-378a-5p inhibitors+FAIM inhibitors(P<0.05).Conclusion MiR-378a-5p silences FAIM,promoting the release of pro-inflammatory factors TNF-α,IL-1,and IL-6 from subcutaneous adipocytes in psoriasis.
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