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miR-455–3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3

Authors :
Hailan He
Jingsi Wang
Yuxi Zhang
Yuan Wang
Yi Liu
Xiang Li
Yingshu Zhang
Jie Yang
Xiaohui Hao
Hongli Wang
Heliang Liu
Source :
Ecotoxicology and Environmental Safety, Vol 278, Iss , Pp 116444- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455–3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455–3p, and miR-455–3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455–3p Inhibitors down-regulated the expression level of miR-455–3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455–3p Mimics showed an opposite trend. These results suggest that miR-455–3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455–3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

Details

Language :
English
ISSN :
01476513
Volume :
278
Issue :
116444-
Database :
Directory of Open Access Journals
Journal :
Ecotoxicology and Environmental Safety
Publication Type :
Academic Journal
Accession number :
edsdoj.16c364e38a64a7ca1146b907578d8de
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ecoenv.2024.116444