{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:36:50Z","timestamp":1778614610422,"version":"3.51.4"},"reference-count":72,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lung epithelial cells play important roles in lung inflammation and injury, although mechanisms remain unclear. Osteopontin (OPN) has essential roles in epithelial damage and repair and in lung cancer biological behaviours. Telocyte (TC) is a type of interstitial cell that interacts with epithelial cells to alleviate acute inflammation and lung injury. The present studies aim at exploring potential mechanisms by which OPN regulates the epithelial origin lung inflammation and the interaction of epithelial cells with TCs in acute and chronic lung injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The lung disease specificity of OPN and epithelial inflammation were defined by bioinformatics. We evaluated the regulatory roles of OPN in OPN\u2010knockdown or over\u2010expressed bronchial epithelia (HBEs) challenged with cigarette smoke extracts (CSE) or in animals with genome OPN knockout (<jats:italic>gKO<\/jats:italic>) or lung conditional OPN knockout (<jats:italic>cKO<\/jats:italic>). Acute lung injury and chronic obstructive pulmonary disease (COPD) were induced by smoking or lipopolysaccharide (LPS). Effects of OPN on PI3K subunits and ERK were assessed using the inhibitors. Spatialization and distribution of OPN, OPN\u2010positive epithelial subtypes, and TCs were defined by spatial transcriptomics. The interaction between HBEs and TCs was assayed by the co\u2010culture system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of OPN expression increased in smokers, smokers with COPD, and smokers with COPD and lung cancer, as compared with healthy nonsmokers. LPS and\/or CSE induced over\u2010production of cytokines from HBEs, dependent upon the dysfunction of OPN. The severity of lung inflammation and injury was significantly lower in OPN\u2010<jats:italic>gKO<\/jats:italic> or OPN\u2010<jats:italic>cKO<\/jats:italic> mice. HBEs transferred with OPN enhanced the expression of phosphoinositide 3\u2010kinase (PI3K)CA\/p110\u03b1, PIK3CB\/p110\u03b2, PIK3CD\/p110\u03b4, PIK3CG\/p110\u03b3, PIK3R1, PIK3R2 or PIK3R3. Spatial locations of OPN and OPN\u2010positive epithelial subtypes showed the tight contact of airway epithelia and TCs. Epithelial OPN regulated the epithelial communication with TCs, and the down\u2010regulation of OPN induced more alterations in transcriptomic profiles than the up\u2010regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data evidenced that OPN regulated lung epithelial inflammation, injury, and cell communication between epithelium and TCs in acute and chronic lung injury. The conditional control of lung epithelial OPN may be an alternative for preventing and treating epithelial\u2010origin lung inflammation and injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1381","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:11:56Z","timestamp":1692684716000},"source":"Crossref","is-referenced-by-count":18,"title":["Regulatory roles of Osteopontin in lung epithelial inflammation and epithelial\u2010telocyte interaction"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-0587","authenticated-orcid":false,"given":"Huirong","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongshan Hospital Fudan University Shanghai Medical College  Shanghai China"},{"name":"Center for Tumor Diagnosis &amp; Therapy Jinshan Hospital Fudan University Shanghai Medical College  Shanghai 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Research for AI Technology for Cardiopulmonary Diseases  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Zhongshan Hospital Fudan University Shanghai Medical College  Shanghai China"},{"name":"Department of Anesthesiology Shanghai Geriatric Medical Center  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Zhongshan Hospital Fudan University Shanghai Medical College  Shanghai China"},{"name":"Center for Tumor Diagnosis &amp; Therapy Jinshan Hospital Fudan University Shanghai Medical College  Shanghai China"},{"name":"Shanghai Institute of Clinical Bioinformatics  Shanghai China"},{"name":"Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases  Shanghai 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