miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κ B/Inflammatory Signaling Pathway
Open accessAbstract
Silica exposure triggers inflammatory response and pulmonary fibrosis that is a severe occupational or environmental lung disease with no effective therapies. The complicated biological and molecular mechanisms underlying silica-induced lung damages have not yet been fully understood. miR-135a inhibits inflammation, apoptosis, and cancer cell proliferation. But the roles of miRNA135a involved in the silica-induced lung damages remain largely unexplored. We investigated the roles and mechanisms of miR-135a underlying silica-induced pulmonary fibrosis. The present study showed silica exposure caused the decrease in miR-135a level but the increase in inflammatory mediators. Transduction of lentivirus expressing miR-135a reduced the level of inflammatory mediators in lung tissues from silica-treated mice and improved pulmonary fibrosis which was consistent with the downregulated α-SMA but enhanced E-cadherin. Moreover, miR-135a overexpression inhibited p-p65 level in lung tissues. Overexpression of miR-135a inhibitor strengthened TLR4 protein level and NF-κB activation in BEAS-2B cells. Injection of PDTC, an inhibitor of NF-κB, further reinforced miR-135a-mediated amelioration of inflammation and pulmonary fibrosis induced by silica. The collective data indicate miR-135a restrains NF-κB activation probably through targeting TLR4 to alleviate silica-induced inflammatory response and pulmonary fibrosis.
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Over-expression of miR-338-3p blocks the ERK/p38MAPK signaling pathway and reduces the expression of pro-inflammatory genes VCAM-1 and ICAM-1RNA.
“Over-expression of miR-338-3p has been shown to block the ERK/p38MAPK signaling pathway and reduce the expression of pro-inflammatory genes VCAM-1 and ICAM-1RNA [43].”
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- Authors
- Xie, B., Lu, C., Chen, C., Zhou, J., & Deng, Z.
- Affiliations
- Central South University (CN)
- Corresponding author
- Deng, Zhenghao
- Venue
- Mediators of Inflammation
- Publisher
- Wiley
- Published
- 2020-06-17
- Volume
- 2020
- Pages
- 1-13
- ISSN
- 0962-9351 (ISSN-L)
- 1466-1861
- PMC
- PMC7317310
- OpenAlex
- W3036016590
- Cited by
- 25
- References
- 57
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 4
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mediators of Inflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Hunan Province (2018JJ2628)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-135a, silica-induced pulmonary fibrosis, NF-κB signaling, TLR4, lung inflammation, microRNA, alpha-smooth muscle actin, E-cadherin, pyrrolidine dithiocarbamate, BEAS-2B cells, occupational lung disease
- MeSH terms
- Animals, Cell Line, Fluorescent Antibody Technique, Lung, Male, Mice, Inbred C57BL, Pulmonary Fibrosis, Silicon Dioxide, Blotting, Western, Signal Transduction, NF-kappa B, MicroRNAs, Mice, Real-Time Polymerase Chain Reaction
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