{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T10:52:59Z","timestamp":1771671179007,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Histone deacetylase (HDAC) has been implicated in rheumatoid arthritis (RA) progression. We investigated the roles of histone deacetylase 3 (HDAC3) involved in RA-associated interstitial lung disease (ILD) fibrosis. Firstly, we measured the expression of HDAC3 and interleukin 17 receptor A (IL17RA) in lung tissue samples from normal controls, idiopathic pulmonary fibrosis (IPF) patients, and RA-ILD patients. Next, chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay were employed to detect the interaction between HDAC3 and microRNA-19a-3p (miR-19a-3p) and between miR-19a-3p and IL17RA. Further, immunohistochemistry was used to localize HDAC3 and IL17RA expression in lung tissues. Additionally, functional assays were conducted followed by expression determination of HDAC3, miR-19a-3p, and IL17RA with reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis. The effect of HDAC3 on RA-ILD in the constructed RA-ILD mouse model was also studied based on arthritis assessment. We found overexpressed HDAC3 and IL17RA as well as silenced miR-19a-3p in RA-ILD mouse model and RA-ILD patients. In the mouse model, HDAC3 downregulated miR-19a-3p in lung fibroblasts to promote the progression of RA-ILD fibrosis. In lung fibroblasts of RA-ILD mice, IL17RA was a target gene of miR-19a-3p. miR-19a-3p negatively regulated IL17RA, thereby increasing the expression of fibrosis markers, COL1A1, COL3A1, and FN, in lung fibroblasts of mice. Taken together, HDAC3 upregulated IL17RA expression by targeting miR-19a-3p to facilitate the RA-ILD fibrosis development, which sheds light on a new HDAC3\/miR-19a-3p\/IL17RA axis functioning in RA-ILD fibrosis.<\/jats:p>","DOI":"10.3389\/fphys.2020.549656","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T06:09:29Z","timestamp":1607062169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Histone Deacetylase 3-Mediated Inhibition of microRNA-19a-3p Facilitates the Development of Rheumatoid Arthritis-Associated Interstitial Lung Disease"],"prefix":"10.3389","volume":"11","author":[{"given":"Hui","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanrong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1136\/thoraxjnl-2015-207439","article-title":"End-of-life care in oxygen-dependent ILD compared with lung cancer: a national population-based study","volume":"71","author":"Ahmadi","year":"2016","journal-title":"Thorax"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1136\/annrheumdis-2015-209064","article-title":"Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes","volume":"76","author":"Angiolilli","year":"2017","journal-title":"Ann. 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