Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production

Fatmah Al-Habeeb, Noof Aloufi, Hussein Traboulsi, Xingxing Liu, Parameswaran Nair, Christina Haston, Ilan Azuelos, Steven K. Huang, Eric S. White, Imed E. Gallouzi, Sergio Di Marco, David H. Eidelman, Carolyn J. Baglole

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 β1 (TGF-β1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-β-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.
Original languageEnglish (US)
Pages (from-to)6836-6851
Number of pages16
JournalJournal of Cellular Physiology
Volume236
Issue number10
DOIs
StatePublished - Oct 1 2021
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2022-09-13

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Clinical Biochemistry

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