miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Integrin alpha6/*genetics ; Lung/*metabolism ; MicroRNAs/*genetics ; Pulmonary Fibrosis/*genetics; Animals ; Cell Cycle/drug effects ; Cell Cycle/genetics ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Disease Models, Animal ; Focal Adhesion Kinase 1/genetics ; Focal Adhesion Kinase 1/metabolism ; Gene Expression Regulation ; Humans ; Integrin alpha6/metabolism ; Lung/drug effects ; Lung/pathology ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/agonists ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/metabolism ; Molecular Mimicry ; NIH 3T3 Cells ; Oligoribonucleotides/genetics ; Oligoribonucleotides/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Pulmonary Fibrosis/chemically induced ; Pulmonary Fibrosis/metabolism ; Pulmonary Fibrosis/prevention & control ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; Silicon Dioxide/administration & dosage ; Transforming Growth Factor beta1/pharmacology

Silicosis is a very serious occupational disease and it features pathological manifestations of inflammatory infiltration, excessive proliferation of fibroblasts and massive depositions of the extracellular matrix in the lungs. Recent studies described the roles of a variety of microRNAs (miRNAs) in fibrotic diseases. Here, we aimed to explore the potential mechanism of miR-542-5p in the activation of lung fibroblasts. To induce a pulmonary fibrosis mouse model, silica suspension and the miR-542-5p agomir were administered to mice by intratracheal instillation and tail vein injection. We found that miR-542-5p was significantly decreased in mouse fibrotic lung tissues and up-regulation of miR-542-5p visually attenuated a series of fibrotic lesions, including alveolar structural damage, alveolar interstitial thickening and silica-induced nodule formation. The down-regulation of miR-542-5p was also observed in mouse fibroblast (NIH-3T3) treated with transforming growth factor β1 (TGF-β1). The proliferation and migration ability of NIH-3T3 cells were also inhibited by the transfection of miR-542-5p mimic. Integrin α6 (Itga6), reported as a cell surface protein associated with fibroblast proliferation, was confirmed to be a direct target of miR-542-5p. The knockdown of Itga6 significantly inhibited the phosphorylation of FAK/PI3K/AKT. In conclusion, miR-542-5p has a potential function for reducing the proliferation of fibroblasts and inhibiting silica-induced pulmonary fibrosis, which might be partially realized by directly binding to Itga6. Our data suggested that miR-542-5p might be a new therapeutic target for silicosis or other pulmonary fibrosis.
Competing Interests: The authors declare no conflict of interest.

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81573119 National Natural Science Foundation of China; 81502796 National Natural Science Foundation of China

Keywords: Silicosis; fibroblast; integrin; miRNA; proliferation

0 (Integrin alpha6)
0 (MIRN542 microRNA, mouse)
0 (MicroRNAs)
0 (Oligoribonucleotides)
0 (RNA, Small Interfering)
0 (Tgfb1 protein, mouse)
0 (Transforming Growth Factor beta1)
7631-86-9 (Silicon Dioxide)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.10.2 (Focal Adhesion Kinase 1)
EC 2.7.10.2 (Ptk2 protein, mouse)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)

Date Created: 20181124 Date Completed: 20190308 Latest Revision: 20200225

20250114

PMC6320929

10.3390/ijms19123717

30467286