Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung

Abstract

Hepatocyte growth factor (HGF) is a mesenchymal‐derived factor which induces mitosis, cell movement and morphogenesis of tissue‐like structure. We analyzed changes in HGF mRNA and its receptor, the c‐met proto‐oncogene product, in the liver, kidney and lung during late fetal and postnatal development in rats. In the liver, the HGF‐mRNA level was very low during late gestation and in neonates, it increased remarkably and reached a maximum two weeks postnatally, to be followed by a decrease to 33% of the maximum. HGF mRNA in the kidney and lung was either undetectable or very low during late gestation and the neonatal period and increased markedly to reach a maximum, respectively, 3–4 weeks postnatally. HGF‐mRNA level in the adult rat lung was fivefold higher than that in the liver and kidney. The number of HGF receptors on plasma membranes of these tissues was low in neonates but there was a rapid increase after birth and a maximum was reached within three weeks. The number of HGF receptors/ng plasma membrane protein at the maximal level was highest in the liver and lowest in the lung. c‐met/HGF‐receptor mRNA in the liver was also low during late‐gestation or in early neonatal periods and increased postnatally. Since HGF‐mRNA and HCF‐receptor levels changed differently in liver, kidney and lung, the expression of HGF and its receptor may be independently regulated in each organ. However, in these organs, HGF mRNA and the HGF receptor increased within a few weeks of birth, HGF may play roles in organ growth, organ maturation and the maintenance of tissue homeostasis during the postnatal period, presumably through its potential to act as mitogen, motogen and morphogen.

Immunolocalization of hepatocyte growth factor and its receptor (c-Met) during mouse liver development

“…In fetal stages, HGF was not detected in our immunoblotting, which may be consistent with the faint signals in northern blot analysis of previous studies using rats (Calvo et al 1996;Hu et al 1993;Kagoshima et al 1992). Immunohistochemically detectable HGF was also weak.…”

Consistent Expression of HGF and c-met in the Perinatal Lung

“…In line with previous reports [23,24] , staining for cmet was detected mostly in bronchial epithelium, in cuboidal cells in sacculi, and in cells apparently representing type II cells in alveolar epithelium. Additional staining for c-met was observed in neutrophils.…”

“…In the developing rat lung, addition of HGF has been shown to stimulate branching morphogenesis both of alveolar and of bronchial epithelia of the fetal rat lung in organ cultures [11] . A rapid postnatal increase in HGF and c-met mRNA has been reported in neonatal rats, suggesting a role for HGF in lung development also postnatally [24] . Our data of consistent protein expression of HGF and c-met during the perinatal period support a role for HGF in lung development in humans also.…”

Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways

“…However, as OSM is expressed in the mid-fetal to perinatal liver and its expression level is signi¢cantly decreased after birth, another factor may be involved in hepatic maturation. It was reported that HGF and c-Met are mainly expressed in the ¢rst few days after birth in rat livers [12]. We therefore examined whether expression of HGF in mouse livers is also detected during postnatal stages.…”

“…These ¢ndings indicate that HGF is an important factor for liver regeneration. It was previously described that mRNAs for HGF and c-Met (the receptor of HGF) were increased at a postnatal stage in several rat tissues such as the liver, lung and kidney [12], suggesting that HGF is involved in the development of these organs.…”