{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:41Z","timestamp":1791576161752,"version":"4.3.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hermansky\u2013Pudlak syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in HPS-1 and HPS-4 patients. However, the mechanisms that underlie the exaggerated injury and fibroproliferative repair responses in HPS have not been adequately defined. In particular, although Galectin-3 (Gal-3) is dysregulated in HPS, its roles in the pathogenesis of HPS have not been adequately defined. In addition, although chitinase 3-like 1 (CHI3L1) and its receptors play major roles in the injury and repair responses in HPS, the ability of Gal-3 to interact with or alter the function of these moieties has not been evaluated. In this article, we demonstrate that Gal-3 accumulates in exaggerated quantities in bronchoalveolar lavage fluids, and traffics abnormally and accumulates intracellularly in lung fibroblasts and macrophages from bleomycin-treated pale ear, HPS-1\u2013deficient mice. We also demonstrate that Gal-3 drives epithelial apoptosis when in the extracellular space, and stimulates cell proliferation and myofibroblast differentiation when accumulated in fibroblasts and M2-like differentiation when accumulated in macrophages. Biophysical and signaling evaluations also demonstrated that Gal-3 physically interacts with IL-13R\u03b12 and CHI3L1, and competes with TMEM219 for IL-13R\u03b12 binding. By doing so, Gal-3 diminishes the antiapoptotic effects of and the antiapoptotic signaling induced by CHI3L1 in epithelial cells while augmenting macrophage Wnt\/\u03b2-catenin signaling. Thus, Gal-3 contributes to the exaggerated injury and fibroproliferative repair responses in HPS by altering the antiapoptotic and fibroproliferative effects of CHI3L1 and its receptor complex in a tissue compartment-specific manner.<\/jats:p>","DOI":"10.4049\/jimmunol.1701442","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T18:10:11Z","timestamp":1517595011000},"page":"2140-2153","source":"Crossref","is-referenced-by-count":64,"title":["Galectin-3 Interacts with the CHI3L1 Axis and Contributes to Hermansky\u2013Pudlak Syndrome Lung Disease"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-6443","authenticated-orcid":false,"given":"Yang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan Hua","family":"He","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-7093","authenticated-orcid":false,"given":"Yueming","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchitra","family":"Kamle","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0130-6947","authenticated-orcid":false,"given":"Chang-min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette R","family":"Gochuico","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"Gahl","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-026X","authenticated-orcid":false,"given":"Barry S","family":"Shea","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital , Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-8557","authenticated-orcid":false,"given":"Jack A","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Brown University , Providence, RI 02912"},{"name":"Department of Internal Medicine, Warren Alpert Medical School of Brown University , Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"2025030610135933100_r1","first-page":"1997","article-title":"Hermansky-Pudlak syndrome","volume-title":"GeneReviews at GeneTests: Medical Genetics Information Resource","author":"Gahl","year":"2012"},{"key":"2025030610135933100_r2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1542\/peds.2012-4003","article-title":"Hermansky-Pudlak syndrome: health care throughout life","volume":"132","author":"Seward","year":"2013","journal-title":"Pediatrics"},{"key":"2025030610135933100_r3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ccm.2016.04.012","article-title":"Hermansky-Pudlak syndrome","volume":"37","author":"El-Chemaly","year":"2016","journal-title":"Clin. 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