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Opposing effects of heparin with TGF‐β or aFGF during repair of a mechanical wound of human endothelium. Influence of cAMP on cell migration
Author(s) -
KleinSoyer Claudine,
Archipoff Gisèle,
Beretz Alain,
Cazenave JeanPierre
Publication year - 1992
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/0248-4900(92)90136-o
Subject(s) - biology , cell growth , intracellular , wound healing , cell migration , microbiology and biotechnology , transforming growth factor , heparin , cell , angiogenesis , endothelial stem cell , endothelium , cancer research , endocrinology , immunology , in vitro , biochemistry
Summary— The effects on vascular wound repair in vitro of aFGF and TGF‐β, growth factors having opposite influences on endothelial cell growth and angiogenesis, were studied using as a model a mechanical lesion of confluent endothelium. Modulation by heparin of the activities of these growth factors during the repair process was also examined. Whereas heparin alone inhibited repair by lowering both cell proliferation and cell migration, TGF‐β alone mainly inhibited cell proliferation. When added together, TGF‐β and heparin exerted a combined inhibitory effect resulting in a residual lesion 50% larger than in controls. aFGF alone accelerated lesion coverage and this effect was enhanced by 40% over control values when heparin was added with aFGF. This acceleration was slightly (less than 10%) but consistently diminished by TGF‐β. Cell density in confluent unwounded areas was increased by 40% in the presence of aFGF, but TGF‐β diminished cell density by 20%. A small (30%) increase in intracellular cAMP was measured whenever aFGF was present during the repair process. In comparison, intracellular cAMP inducing agents (forskolin, dbcAMP) accelerated cell migration by 20% during lesion recovery without affecting cell proliferation or density. The present results show that the inhibitory effects of TGF‐β during vascular wound repair are opposed by aFGF. Furthermore, heparin (or heparan sulfates in vivo ) modulates growth factors having activating or inhibiting functions and thus plays a regulatory role during the repair process. cAMP‐inducing substances other than growth factors are able to accelerate cell migration.