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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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
Externally publishedYes

Fingerprint

Proteolysis
Lipoprotein Receptors
Collagen
Plasminogen Activators
Urokinase-Type Plasminogen Activator
Proteins
Interleukin-1
Low Density Lipoprotein Receptor-Related Protein-1
Urokinase Plasminogen Activator Receptors
Interleukin-1 Receptors
Cells
Cytokines
Ligands
Messenger RNA
Processing

Keywords

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

ASJC Scopus subject areas

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

Cite this

Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells. / Tucker, Torry A.; Williams, LaTerrica; Koenig, Kathleen; Kothari, Hema; Komissarov, Andrey A.; Florova, Galina; Mazar, Andrew P.; Allen, Timothy C.; Bdeir, Khalil; Rao, L. Vijaya Mohan; Idell, Steven.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 46, No. 2, 01.02.2012, p. 196-206.

Research output: Contribution to journalArticle

Tucker, TA, Williams, L, Koenig, K, Kothari, H, Komissarov, AA, Florova, G, Mazar, AP, Allen, TC, Bdeir, K, Rao, LVM & 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, vol. 46, no. 2, pp. 196-206. https://doi.org/10.1165/rcmb.2011-0071OC
Tucker, Torry A. ; Williams, LaTerrica ; Koenig, Kathleen ; Kothari, Hema ; Komissarov, Andrey A. ; Florova, Galina ; Mazar, Andrew P. ; Allen, Timothy C. ; Bdeir, Khalil ; Rao, L. Vijaya Mohan ; Idell, Steven. / Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells. In: American Journal of Respiratory Cell and Molecular Biology. 2012 ; Vol. 46, No. 2. pp. 196-206.
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