miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway
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 inhib...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/1231243 |
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| _version_ | 1832566107977809920 |
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| author | Bin Xie Can Lu Chen Chen Jianhua Zhou Zhenghao Deng |
| author_facet | Bin Xie Can Lu Chen Chen Jianhua Zhou Zhenghao Deng |
| author_sort | Bin Xie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0281e0f0b3ba4b59b532f30fc9acfdd6 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0281e0f0b3ba4b59b532f30fc9acfdd62025-02-03T01:05:02ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/12312431231243miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling PathwayBin Xie0Can Lu1Chen Chen2Jianhua Zhou3Zhenghao Deng4Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaSilica 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.http://dx.doi.org/10.1155/2020/1231243 |
| spellingShingle | Bin Xie Can Lu Chen Chen Jianhua Zhou Zhenghao Deng miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway Mediators of Inflammation |
| title | miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway |
| title_full | miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway |
| title_fullStr | miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway |
| title_full_unstemmed | miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway |
| title_short | miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-κB/Inflammatory Signaling Pathway |
| title_sort | mir 135a alleviates silica induced pulmonary fibrosis by targeting nf κb inflammatory signaling pathway |
| url | http://dx.doi.org/10.1155/2020/1231243 |
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