COLLAGEN MATRICES ATTENUATE THE COLLAGEN-SYNTHETIC RESPONSE OF CULTURED FIBROBLASTS TO TGF-BETA

Transforming growth factor-beta, a potent modulator of cell function, induces fibroblasts cultured on plastic to increase collagen synthesis , In 5- and 7-day porcine skin wounds, which have minimal to moderate collagen matrix, respectively, transforming growth factor-beta and typ e I procollagen were coordinately expressed throughout the granulation tissue, However, in 10-day collagen-rich granulation tissue type I pr ocollagen expression diminished despite persistence of transforming gr owth factor-beta. To investigate whether collagen matrix attenuates th e collagen-synthetic response of fibroblasts to transforming growth fa ctor-beta, we cultured human dermal fibroblasts in conditions that sim ulate collagen-rich granulation tissue. Therefore, human dermal fibrob lasts were suspended in attached collagen gels and collagen and noncol lagen production was assayed in the absence and presence of transformi ng growth factor-beta. Although transforming growth factor-beta stimul ated collagen synthesis by fibroblasts cultured in the collagen gels, these fibroblasts consistently produced less collagen than similarly t reated fibroblasts cultured on plastic, This phenomenon was not second ary to nonspecific binding of transforming growth factor-beta to the c ollagen matrix, Fibroblasts cultured in a fibrin gel responded to tran sforming growth factor-beta similarly to fibroblasts cultured on plast ic, Using immunofluorescence probes to type I procollagen, we observed that transforming growth factor-beta increased type I procollagen exp ression in most fibroblasts cultured on plastic, but only in occasiona l fibroblasts cultured in collagen gels. From these data we conclude t hat collagen matrices attenuate the collagen synthetic response of fib roblast to transforming growth factor-beta in vitro and possibly in vi vo.