Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells

Torry A. Tucker, La Terrica Williams, Kathleen Koenig, Hema Kothari, Andrey A. Komissarov, Galina Florova, Andrew P. Mazar, Timothy C. Allen, Khalil Bdeir, L. Vijaya Mohan Rao, Steven Idell

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The low-density lipoprotein receptor-related protein 1 (LRP-1) binds and can internalize a diverse group of ligands, including members of the fibrinolytic pathway, urokinase plasminogen activator (uPA), and its receptor, uPAR. In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis, and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the proinflammatory cytokines TNF-α and IL-1β, LRP-1 significantly decreased at the mRNA and protein levels (70 and 90%, respectively; P <, 0.05). Consequently, uPA-mediated uPAR internalization was reduced by 80%in the presence of TNF-α or IL-1β (P< 0.05). In parallel studies, LRP-1 neutralization with receptor-associated protein (RAP) significantly reduced uPA-dependent uPAR internalization and increased uPAR stability in PMCs. LRP-1-deficient cells demonstrated increased uPAR t 1/2 versus LRP-1-expressing PMCs. uPA enzymatic activity was also increased in LRP-1-deficient and neutralized cells, and RAP potentiated uPA-dependent migration in PMCs. Collagen expression in PMCs was also induced by uPA, and the effect was potentiated in RAP-treated cells. These studies indicate that TNF-α and IL-1β regulate LRP-1 in PMCs and that LRP-1 thereby contributes to a range of pathophysiologically relevant responses of these cells.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2012

Keywords

  • Half-life
  • Internalization
  • LRP-1
  • Pleural mesothelial cells
  • uPAR

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Tucker, T. A., Williams, L. T., Koenig, K., Kothari, H., Komissarov, A. A., Florova, G., Mazar, A. P., Allen, T. C., Bdeir, K., Rao, L. V. M., & Idell, S. (2012). Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells. American journal of respiratory cell and molecular biology, 46(2), 196-206. https://doi.org/10.1165/rcmb.2011-0071OC