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Extracellular matrix is a source of mitogenically active platelet-derived growth factor
S L Field1, L M Khachigian, M J Sleigh
1Centre for Thrombosis and Vascular Research, School of Pathology, Prince of Wales Hospital, University of New South Wales, Sydney, Australia.
Journal of Cellular Physiology
|August 1, 1996
Summary
Platelet-derived growth factor (PDGF) stored in the extracellular matrix can stimulate cell growth. Different cell types utilize matrix-bound PDGF through distinct mechanisms, impacting proliferation and disease.
Area of Science:
- Cell Biology
- Biochemistry
- Developmental Biology
Background:
- Platelet-derived growth factor (PDGF) is crucial for fibroblast and smooth muscle cell proliferation and implicated in atherosclerosis.
- PDGF exists as A and B polypeptide dimers, with different isoforms exhibiting varied localization (secreted, matrix-associated, or cell/medium-bound).
Purpose of the Study:
- To investigate the mitogenic potential of matrix-localized PDGF on different cell types.
- To elucidate the mechanisms by which cells access and respond to extracellular matrix-bound PDGF.
Main Methods:
- Culturing Balb/c-3T3 cells, human foreskin fibroblasts, and rabbit aortic smooth muscle cells on extracellular matrix (ECM) from PDGF-expressing Chinese hamster ovary (CHO) cells and human umbilical vein endothelial cells (HUVEC).
- Assessing cell proliferation in response to matrix-localized PDGF.
- Investigating the role of proteolytic activity (plasminogen activator, metalloproteinase, serine protease) in PDGF utilization.
Main Results:
- Fibroblasts and smooth muscle cells demonstrated mitogenic responses to PDGF immobilized in the ECM.
- Balb/c-3T3 cells required proteolytic activity, specifically plasminogen activator, to utilize matrix-bound PDGF.
- Human foreskin fibroblasts and smooth muscle cells accessed matrix-localized PDGF through direct contact without apparent need for proteolytic enzymes.
Conclusions:
- Matrix-localized PDGF serves as a potent local growth stimulus for various cell types.
- Cellular mechanisms for accessing matrix-bound PDGF differ, involving either proteolytic degradation or direct matrix interaction.
- Understanding these mechanisms is vital for developing therapies targeting excessive cell proliferation in diseases like atherosclerosis.