To examine the effect of hepatocyte growth factor (HGF) and fibroblast growth factor-1(FGF-1) on the regeneration of submandibular gland (SMG), rat SMG (RSMG) epithelial cells were primary cultured in serum-free medium. FGF-1 and HGF individually promoted the proliferation of RSMG cells in a dose-dependent manner, and FGF-1 remarkably promoted the proliferation effect of HGF. In three-dimensional collagen gel culture, RSMG cells were able to form branching structures. HGF potently induced branching morphogenesis of RSMG cell colonies embedded in collagen gel. RSMG cells treated with FGF-1 grew into a star-like colonies, but not further. However, FGF-1 remarkably promotes the morphogenic effect of HGF, assuring that the colony cultured in the presence of both FGF-1 and HGF formed more branches than colonies growing in the presence of only one growth factor. Paraffin section of the RSMG cells embedded in collagen gel revealed well-formed lumina in the presence of HGF and FGF-1. This morphology resembles closely the one found in situ. These findings suggest that HGF induces the proliferation and branching morphogenesis, and FGF-1 enhances the effect of HGF in the SMG regeneration. hepatocyte growth factor, fibroblast growth factor, salivary gland, morphogenesis, regeneration
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