{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:06:05Z","timestamp":1789625165965,"version":"build-2803163510"},"reference-count":46,"publisher":"American Physiological Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:p> Chronic allergic asthma leads to airway remodeling and subepithelial fibrosis via mechanisms not fully understood. Airway remodeling is amplified by profibrotic mediators, such as transforming growth factor-\u03b21 (TGF-\u03b21), which plays a cardinal role in various models of fibrosis. We recently have identified a critical role for c-Jun-NH<jats:sub>2<\/jats:sub>-terminal-kinase (JNK) 1 in augmenting the profibrotic effects of TGF-\u03b21, linked to epithelial-to-mesenchymal transition of airway epithelial cells. To examine the role of JNK1 in house dust mite (HDM)-induced airway remodeling, we induced allergic airway inflammation in wild-type (WT) and JNK1\u2212\/\u2212 mice by intranasal administration of HDM extract. WT and JNK1\u2212\/\u2212 mice were sensitized with intranasal aspirations of HDM extract for 15 days over 3 wk. HDM caused similar increases in airway hyperresponsiveness, mucus metaplasia, and airway inflammation in WT and JNK1\u2212\/\u2212 mice. In addition, the profibrotic cytokine TGF-\u03b21 and phosphorylation of Smad3 were equally increased in WT and JNK1\u2212\/\u2212 mice. In contrast, increases in collagen content in lung tissue induced by HDM were significantly attenuated in JNK1\u2212\/\u2212 mice compared with WT controls. Furthermore HDM-induced increases of \u03b1-smooth muscle actin (\u03b1-SMA) protein and mRNA expression as well as the mesenchymal markers high-mobility group AT-hook 2 and collagen1A1 in WT mice were attenuated in JNK1\u2212\/\u2212 mice. The let-7 family of microRNAs has previously been linked to fibrosis. HDM exposure in WT mice and primary lung epithelial cells resulted in striking decreases in let-7g miRNA that were not observed in mice or primary lung epithelial cells lacking JNK1\u2212\/\u2212 mice. Overexpression of let-7g in lung epithelial cells reversed the HDM-induced increases in \u03b1-SMA. Collectively, these findings demonstrate an important requirement for JNK1 in promoting HDM-induced fibrotic airway remodeling. <\/jats:p>","DOI":"10.1152\/ajplung.00153.2013","type":"journal-article","created":{"date-parts":[[2014,3,8]],"date-time":"2014-03-08T05:01:19Z","timestamp":1394254879000},"page":"L866-L875","source":"Crossref","is-referenced-by-count":24,"title":["Absence of c-Jun NH<sub>2<\/sub>-terminal kinase 1 protects against house dust mite-induced pulmonary remodeling but not airway hyperresponsiveness and inflammation"],"prefix":"10.1152","volume":"306","author":[{"given":"Jos L. 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