Role of fibronectin as a growth factor for fibroblasts.

Abstract

Fibroblast replication is regulated by exogenous signals provided by growth factors, mediators that interact with the target cell surface and signal the cell to proliferate . A useful model of growth regulation, the "dual control model," suggests that growth factors can be grouped either as competence factors or as progression factors, and that optimal replication of fibroblasts requires the presence of both types of growth factors . Although most growth factors are soluble mediators, recent studies have demonstrated that, for some cell types, the extracellular matrix can replace the requirement for a competence factor . Since fibronectin is an important constituent of the extracellular matrix that interacts with specific domains on the fibroblast surface, we examined the ability of fibronectin to act as a competence factor to promote the growth of human diploid fibroblasts. To accomplish this, fibronectins purified from two sources, human plasma and human alveolar macrophages, were tested for their ability to (a) stimulate fibroblast replication in serum-free medium containing characterized progression factors (insulin or alveolar macrophage-derived growth factor) ; (b) provide a growth-promoting signal early in G, . Fibronectin stimulated fibroblast replication in a closedependent manner in the presence of a fixed dose of a progression factor . Conversely, fibronectin conferred on previously unresponsive fibroblasts the ability to replicate in a closedependent manner when cultured with increasing amounts of a progression factor. Moreover, fibronectin signaled growth-arrested fibroblasts to traverse G,^-4 h closer to S phase. No differences were observed in the ability of plasma or macrophage fibronectins to provide a competence signal for fibroblast replication . Since fibronectin is a major component of the extracellular matrix, these observations suggest that it may provide at least one of the signals by which the matrix conveys the "competence" that permits fibroblasts to replicate in the presence of an appropriate progression signal.Fibroblast replication requires exogenous growth factors, mediators acting with temporal specificity in the G, phase of the cell cycle to promote DNA synthesis and cell replication (1-5). Analysis of this temporal specificity has led to the hypothesis that there are two major categories of growth factors, competence factors, and progression factors (5, 6). Competence factors, such as fibroblast growth factor or plateletderived growth factor, act early in G,, rendering the cell responsive, for a variable number of hours, to progression factors (7) . Progression factors, such as insulin, insulin-like growth factors, and alveolar macrophage-derived growth factor, act later in G,, signaling the cell to continue through the cell cycle and replicate (7,8). Both categories ofgrowth factors are thought to provide their signals to the target cell by interaction with specific cell surface receptors . Moreover, as THE JOURNAL OF CELL BIOLOGY " VOLUME 97 DECEMBER 1983 1925-1932 C ...

Two-Hour Methyl Isocyanate Inhalation and 90-Day Recovery Study in B6C3F1 Mice

“…These glands may provide a protected reserve cell for a more rapid epithelialization of the trachea before migration of the fibroblasts could occur. Thirdly, the lung may contain more chemotactic factors than the trachea which may enhance the migration of fibroblasts through epithelial defects (14,15) leading to intraluminal fibrosis. Whether the lesion found in the MIC-exposed mice is analogous to the intraluminal fibrosis seen in a variety of conditions in man is not known.…”

Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats.

“…a chemotactic factor for fibroblasts that also appears to play a role in fibroblast replication (Bitterman et al, 1983). The production of growth factors by activated alveolar macrophages and the resulting effects of these factors on mesenchymal cells are likely to be important links between macrophage recruitment and interstitial fibrosis.…”

Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene.

“…The mechanism underlying the pathogenesis of the disease is still unclear. Several factors have been shown to influence the accumulation of interstitial extracellular matrix in the lung (11)(12)(13)(14)(15)(16). Lazo and Humphreys (17) have also suggested that the lack of bleomycin hydrolase activity in the lung may contribute to the development of bleomycin-induced pulmonary fibrosis.…”