Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid mediator and important component of serum. Studies over the past several years which have documented diverse effects of LPA on multiple types of airway cells and which suggest possible involvement of LPA in lung disease are reviewed here. LPA enhances contractility of airway smooth muscle. It also stimulates proliferation of cultured airway smooth muscle cells and exhibits a striking synergism with epidermal growth factor (EGF) for stimulating mitogenesis. Recent studies of the molecular components and signaling pathways mediating synergism are described, including LPA-induced upregulation of EGF receptors and activation of multiple transcription factors by both LPA and EGF. A model for the effects of LPA and EGF on mitogenesis that includes EGF receptor upregulation and synergism between Ras and Rho for activation of the transcription factor AP-1 is presented. LPA stimulates fibronectin secretion and filopodia extension in airway epithelial cells as well as proliferation and collagen gel contraction by lung fibroblasts. A hypothesis for LPA involvement in the airway repair and remodeling, which contribute to the pathology of asthma and other airway diseases, is presented, and future directions for research into the roles of LPA in airway function and disease are suggested.

Original languageEnglish (US)
Pages (from-to)240-250
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1582
Issue number1-3
DOIs
StatePublished - May 23 2002

Fingerprint

Epidermal Growth Factor
Up-Regulation
lysophosphatidic acid
Airway Remodeling
Pseudopodia
Transcription Factor AP-1
Fibronectins
Epidermal Growth Factor Receptor
Lung Diseases
Smooth Muscle Myocytes
Smooth Muscle
Transcription Factors
Collagen
Asthma
Fibroblasts
Gels
Epithelial Cells
Pathology
Lipids
Lung

Keywords

  • Airway smooth muscle
  • Asthma
  • Contraction
  • Lung
  • Lysophosphatidic acid
  • Mitogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lysophosphatidic acid in airway function and disease. / Toews, Myron Lee; Ediger, Tracy L.; Romberger, Debra; Rennard, Stephen I.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1582, No. 1-3, 23.05.2002, p. 240-250.

Research output: Contribution to journalReview article

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