Structure and activation of the large latent transforming growth factor-Beta complex.
BACKGROUND
Many cytokines regulate processes involved in the pathogenesis of proliferative vitreoretinopathy. Transforming growth factor-beta (TGF-beta) is an example of a pluripotent growth factor that regulates cell proliferation, extracellular matrix (ECM) deposition, cell migration, and differentiation--all biological activities involved in the formation and progression of proliferative vitreoretinopathies.


METHODS
A review of experimental results that demonstrate how vascular cells generate biologically active TGF-beta is presented. Most cell types--including endothelial cells and pericytes, which form the retinal microvasculature--express TGF-beta as a large latent TGF-beta complex. Mature TGF-beta, the biologically active form, must be generated from the large latent complex before it can signal by binding to its high affinity cell surface receptors.


RESULTS
A critical step in regulating TGF-beta effects may be the activation of the large latent TGF-beta complex. Activation of the complex can be achieved by chemical and enzymatic treatments, or by various cell systems. We have identified that co-culturing bovine smooth muscle cells or pericytes and endothelial cells generates active TGF-beta.


CONCLUSIONS
The mechanism of latent TGF-beta activation self-regulates through effectors of plasmin generation. Studying TGF-beta generation by co-cultures of pericytes and endothelial cells can provide us with insights into how disruption of latent TGF-beta activation may lead to unregulated endothelial proliferation, ECM deposition, and cellular infiltration, as observed clinically in neovascular- and fibrotic-related pathologies.
Nunes
I
I
Department of Cell Biology, New York University Medical Center, New York, USA.
Munger
J
J
Harpel
J G
JG
Nagano
Y
Y
Shapiro
R
R
Gleizes
P E
PE
Rifkin
D B
DB
D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry* / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology
D008562:Membrane Glycoproteins; D017468:Receptors, Fibroblast Growth Factor