{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:17:36Z","timestamp":1774477056113,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"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":[[2014,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The etiology of Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis (HPSPF), a progressive interstitial lung disease with high mortality, is unknown. Galectin-3 is a \u03b2-galactoside\u2013binding lectin with profibrotic effects. The objective of this study was to investigate the involvement of galectin-3 in HPSPF. Galectin-3 was measured by ELISA, immunohistochemistry, and immunoblotting in human specimens from subjects with HPS and control subjects. Mechanisms of galectin-3 accumulation were studied by quantitative RT-PCR, Northern blot analysis, membrane biotinylation assays, and rescue of HPS1-deficient cells by transfection. Bronchoalveolar lavage galectin-3 concentrations were significantly higher in HPSPF compared with idiopathic pulmonary fibrosis or that from normal volunteers, and correlated with disease severity. Galectin-3 immunostaining was increased in HPSPF compared with idiopathic pulmonary fibrosis or normal lung tissue. Fibroblasts from subjects with HPS subtypes associated with pulmonary fibrosis had increased galectin-3 protein expression compared with cells from nonfibrotic HPS subtypes. Galectin-3 protein accumulation was associated with reduced Galectin-3 mRNA, normal Mucin 1 levels, and up-regulated microRNA-322 in HPSPF cells. Membrane biotinylation assays showed reduced galectin-3 and normal Mucin 1 expression at the plasma membrane in HPSPF cells compared with control cells, which suggests that galectin-3 is mistrafficked in these cells. Reconstitution of HPS1 cDNA into HPS1-deficient cells normalized galectin-3 protein and mRNA levels, as well as corrected galectin-3 trafficking to the membrane. Intracellular galectin-3 levels are regulated by HPS1 protein. Abnormal accumulation of galectin-3 may contribute to the pathogenesis of HPSPF.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0025oc","type":"journal-article","created":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T16:50:31Z","timestamp":1382028631000},"page":"605-613","source":"Crossref","is-referenced-by-count":46,"title":["Dysregulation of Galectin-3. Implications for Hermansky-Pudlak Syndrome Pulmonary Fibrosis"],"prefix":"10.1093","volume":"50","author":[{"given":"Andrew R.","family":"Cullinane","sequence":"first","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Yeager","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Dorward","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelo","family":"Carmona-Rivera","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research 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