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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 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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