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Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production.
Al-Habeeb, Fatmah; Aloufi, Noof; Traboulsi, Hussein; Liu, Xingxing; Nair, Parameswaran; Haston, Christina; Azuelos, Ilan; Huang, Steven K; White, Eric S; Gallouzi, Imed E; Di Marco, Sergio; Eidelman, David H; Baglole, Carolyn J.
Afiliación
  • Al-Habeeb F; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Aloufi N; Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Traboulsi H; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Liu X; Departments of Pathology, McGill University, Montreal, Quebec, Canada.
  • Nair P; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Haston C; Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Azuelos I; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Huang SK; Department of Medicine, McMaster University & St Joseph's Healthcare, Hamilton, Ontario, Canada.
  • White ES; Department of Computer Science, Mathematics, Physics and Statistics, University of British Columbia, British Columbia, Canada.
  • Gallouzi IE; Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  • Di Marco S; Department of Medicine, McGill University, Montreal, Quebec, Canada.
  • Eidelman DH; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Baglole CJ; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
J Cell Physiol ; 236(10): 6836-6851, 2021 10.
Article en En | MEDLINE | ID: mdl-33855709
Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α-SMA-expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor ß1 (TGF-ß1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-ß-treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α-SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Matriz Extracelular / Transdiferenciación Celular / Fibrosis Pulmonar Idiopática / Miofibroblastos / Fibroblastos / Proteína 1 Similar a ELAV / Pulmón Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Matriz Extracelular / Transdiferenciación Celular / Fibrosis Pulmonar Idiopática / Miofibroblastos / Fibroblastos / Proteína 1 Similar a ELAV / Pulmón Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Physiol Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos