Effect of miR-455-3p targeting regulation of VEGF-C on lymphangiogenesis in silicosis

Acta Universitatis Medicinalis Anhui     font:big middle small

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Authors:Wang Jingsi, Zhang Menglu, Cui Jie, He Hailan, Liu Yi, Guo Lingli, Hao Xiaohui, Liu Heliang

Keywords:miR-455-3p;VEGF-C;silicosis;lymphangiogenesis

DOI:10.19405/j.cnki.issn1000-1492.2023.09.015

〔Abstract〕 Objective To explore the regulatory role of microRNA-455-3p(miR-455-3p) in lymphangiogenesis of rat silicosis model,and to investigate the effect of miR-455-3p targeted regulation of vascular endothelial growth factor C(VEGF-C) on the tubular structure formation of human lymphatic endothelial cells(HLECs).Methods The rats were randomly divided into the silicosis model group and the normal control group.The silicosis model group were injected with silicon dioxide(SiO2) dust suspension,and the control group was injected with the same amount of normal saline.HE,Masson and immunohistochemistry staining were used to observe the pathological changes and lymphangiogenesis of lung tissue.The expression levels of miR-455-3p and VEGF-C in lung tissues of rats were detected by Quantitative real-time PCR(RT-qPCR) and Western blot;The miR-455-3p inhibitors and negative controls(NC) were transfected into HLECs,and the expression levels of miR-455-3p and VEGF-C in cells were detected by RT-qPCR and Western blot.The migration ability of HLECs was detected by scratch test,the ability of tubular structure formation was detected by matrigel tube formation test,and dual luciferase experiments were used to verify the targeting relationship between miR-455-3p and VEGF-C.Results Compared with the normal control group,in the silicosis model group,a large number of inflammatory cells gathered and collagen gradually deposited in the pulmonary interstitium,and there was lymphatic hyperplasia in the lung.The expression of miR-455-3p in the lung tissue was lower than that in the control group,and the expression of VEGF-C was higher than that in the control group;After transfection with HLECs,compared with the NC group,the expression of miR-455-3p in the cells of the Inhibitors group decreased,the expression of VEGF-C increased,and the ability of cell migration and tubular structure formation increased(P<0.05);VEGF-C was confirmed as a target gene of miR-455-3p by the dual luciferase experiments.Conclusion miR-455-3p can affect the tubular structure formation ability of HLECs and regulate lymphangiogenesis by targeting the expression of VEGF-C.