Abstract
Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and renotropic functions for regeneration of the liver and kidney through its mitogenic, motogenic, and morphogenic properties. To examine the involvement of HGF in lung regeneration after acute injury, we analyzed changes of HGF mRNA, HGF activity, and HGF receptors in the rat lung after lung insult and measured HGF concentration in sera of patients with various lung diseases. Following the onset of acute lung injury induced by intratracheal hydrochloride injection, a compensatory DNA synthesis occurred in the bronchial epithelium with a peak at 24 h and in the alveolar epithelium with a peak at 48 h. Expression of HGF mRNA in the rat lung remarkably increased only 3 h after the treatment and HGF activity in the lung also increased to about 3-fold at 6 h later. HGF receptors in the lung but not in the other noninjured organs were down-regulated 12 h later. These marked increases in HGF mRNA and HGF activity and the concomitant down-regulation of HGF receptor occurred before the marked compensatory DNA synthesis in bronchial and alveolar epithelial cells. HGF concentration in sera of patients with various lung diseases, as measured by radioimmunoassay, was much higher than that in healthy donors. These results suggest that HGF is newly produced in the lung after acute lung injury and may have a role in regeneration of the lung.
Highlights
Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and renotropficunctionsfor regeneration of the liver and kidney through its mitogenic, motogenic, and morphogenic propertieTso. examinethe involvement ofHGF in lung regeneration after acute mains in the a-chain and the serine protease-like doinmtahien P-chain [10,11,12,13]
HGF mRNA and HGF activity andtheconcomitant jected recombinant HGF markedly enhancleisver regeneration down-regulation ofHGF receptor occurred before the marked compensatory DNA synthesis in bronchial and alveolar epithelial cells
We described here evidence that both HGF mRNA and HGF activity markedly increasedfollowed by marked down-regulation of the HGFreceptor and subsequentlyby DNA synthesis of lungepithelial cells intheinjuredlung.Our findings lend support to the thesis that HGF mbeaya “pulmotrophic factor” for regeneration of an injured lung
Summary
Assay for HGFActiuity-HGF activity was determined by measuring the stimulatory effect on DNA synthesis of rat hepatocytes in primary chial epithelia (Fig. 2 A ) and alveolar type I1 epithelial cells in alveolar septa, characterized by a round nucleus and a comparatively small cytosol protruding into the alveolar space (Fig. 2 B ). The number of cells undergoing DNA synthesis in the bronchial epithelia and the alveolar septa remarkably increased from 24 h following HCltreatment (Fig. 3). Time courses of DNA synthesis in bronchial and alveolar epithelial cells in rat lung after HC1-induced injury. Produced at the injured site and other intact organs such as Change in Binding of I2'jl-HGF to the Plasma Membranes lung, spleen, and kidney [29,38,39] exertsbiological activities. Since down- the lungsubjected to insultis involved in lung regenerationw,e
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
