Hepatocyte growth factor activator: A possible regulator of morphogenesis during fetal development of the rat gastrointestinal tract

The role played by the hepatocyte growth factor activator (HG;FA) during mo rphogenesis of the gastrointestinal tract was investigated in fetal rats be tween days 16 and 21 of gestation. By our recently established method using chelation and dissecting microscope, samples could be separated into epith elium and mesenchyme, essentially without cross-contamination. The expressi on of the gene for HG;FA together with those for hepatocyte growth factor ( HGF) and its receptor, c-met, was investigated in each tissue element by RT -PCR. In the fetal rat gastrointestinal tract, mRNA signals for the HGFA ge ne were observed only in epithelia expressing c-met mRNA. In contrast, expr ession of HGF mRNA was limited to the mesenchymal elements, indicating the presence of a local HGF system in the gastrointestinal tract; an inactive f orm of HGF (proHGF) is secreted from the mesenchyme and then cleaved into t he active form by HGFA secreted by the target epithelia. During the period of morphogenesis and histodifferentiation in the gastrointestinal tract, en hanced expression of the genes for HGF and its receptor/c-met was evident, with elevated HGFA mRNA level observed throughout the gastrointestinal trac t except in the forestomach, where mRNA expression was barely detectable. T hese results strongly suggest the possibility that morphogenesis of the gas trointestinal tract is regulated not only by a local increase in production of HGF, but also by enhanced proteolytic activation of proHGF. Thus, it is probable that locally synthesized HGFA plays a significant role as a regul ator of the morphogenic action of HGF during gastrointestinal tract develop ment. (C) 1998 Academic Press.