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Galectin-3 Interacts with the CHI3L1 Axis and Contributes to Hermansky-Pudlak Syndrome Lung Disease.
Zhou, Yang; He, Chuan Hua; Yang, Daniel S; Nguyen, Tung; Cao, Yueming; Kamle, Suchitra; Lee, Chang-Min; Gochuico, Bernadette R; Gahl, William A; Shea, Barry S; Lee, Chun Geun; Elias, Jack A.
Afiliación
  • Zhou Y; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; jack_elias@brown.edu yang_zhou@brown.edu.
  • He CH; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Yang DS; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Nguyen T; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Cao Y; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Kamle S; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Lee CM; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Gochuico BR; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
  • Gahl WA; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
  • Shea BS; Division of Pulmonary, Critical Care and Sleep Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903; and.
  • Lee CG; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912.
  • Elias JA; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; jack_elias@brown.edu yang_zhou@brown.edu.
J Immunol ; 200(6): 2140-2153, 2018 03 15.
Article en En | MEDLINE | ID: mdl-29427412
Hermansky-Pudlak 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-deficient 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-13Rα2 and CHI3L1, and competes with TMEM219 for IL-13Rα2 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/ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Hermanski-Pudlak / Galectina 3 / Proteína 1 Similar a Quitinasa-3 / Pulmón Límite: Animals Idioma: En Revista: J Immunol Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Hermanski-Pudlak / Galectina 3 / Proteína 1 Similar a Quitinasa-3 / Pulmón Límite: Animals Idioma: En Revista: J Immunol Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos