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Differential response to transforming growth factors-β1 and β2: connective tissue deposition in animal models
Authors:Yasushi Ogawa,PhD,   Carolyn O. Gerhardt,BA,   George A. Ksander,MA
Affiliation:Celtrix Pharmaceuticals, Santa Clara, California 95054, USA.
Abstract:The ability of transforming growth factor (TGF)-beta(1) and TGF-beta(2) to promote connective tissue deposition were compared in different animal models. A single subcutaneous injection of TGF-beta(2) in collagen/heparin gel carrier promoted markedly more extensive development of connective tissue than TGF-beta(1) at the site of injection in both neonatal and adult mice. Both TGF-beta(1) and TGF-beta(2) promoted deposition of dense and well-vascularized connective tissue matrix infiltrated with macrophages and fibroblasts. However, the results of immunohistochemical analyses suggested that TGF-beta(2) promoted an accumulation of more macrophages in the connective tissue than TGF-beta(1). Similar differences in the extent of connective tissue development were observed in neonatal mice when these factors were administered as a solution, without the collagen/heparin gel carrier. TGF-beta(2) was also more potent than TGF-beta(1) in domestic pigs. However, in guinea pigs, TGF-beta(1) promoted more extensive connective tissue development than TGF-beta(2). These results suggest that the differential connective tissue response to TGF-beta(1) and TGF-beta(2) is species dependent. However, the differences in the physical and chemical properties of these factors may account in part for the differential response as well.
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