Hepatocyte growth factor inhibits the formation of the basement membrane of alveolar epithelial cells in vitro

Abstract

Furuyama, Akiko, and Katsumi Mochitate. Hepatocyte growth factor inhibits the formation of the basement membrane of alveolar epithelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 286: L939-L946, 2004. First published December 12, 2003 10.1152/ ajplung.00238.2002-Hepatocyte growth factor (HGF) is a pulmotrophic factor for the regeneration of injured pulmonary tissue. We investigated the role of HGF in basement membrane formation during wound healing by immortalized alveolar type II epithelial cells that could form a continuous basement membrane when they were cultured on collagen fibrils in the presence of entactin-contaminated laminin-1. Cells cultured with 5.0 ng/ml HGF neither formed a continuous basement membrane on collagen fibrils nor maintained a continuous basement membrane architecture on a basement membrane substratum. The cells showed increased secretion of matrix metalloproteinase-9 and urokinase-type plasminogen activator, and the HGF-induced inhibition of basement membrane formation was attenuated by addition of 200 ng/ml tissue inhibitor of matrix metalloproteinase-1. Cells sequentially exposed to HGF and 1.0 ng/ml transforming growth factor-␤1 had enhanced basement membrane formation compared with those receiving these reagents in the reverse order or concurrently. HGF simultaneously stimulated proliferation and migration of the cells so that it advanced wound closure on the basement membrane substratum. The present results indicate that the role of HGF in wound healing is the stimulation of reepithelization, but this factor may also contribute to the degradation of the basement membrane. wound healing; matrix metalloproteinase-9; urokinase-type plasminogen activator; lamina densa; transforming growth factor-␤1

Epithelial repair mechanisms in the lung

“…HGF is a known mitogen for rat ATII cells in vitro (104) and in vivo (117). HGF inhibited the formation of basement membrane and stimulated both proliferation and migration of immortalized ATII cells (46); however, HGF increased cell migration but not proliferation during human nasal epithelial repair in vitro (199), suggesting that epithelial cells from different locations may display differing responses to HGF. Takami et al (162) reported that HGF stimulated proliferation of a human bronchial epithelial cell line (BEAS-2B) and that the MEK-ERK signaling pathway was necessary but not sufficient for this stimulation.…”

Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling

“…The HGF/c-Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis (40). HGF is a mitogen for rat ATII cells in vitro (34), and HGF stimulates both proliferation and migration of immortalized rat ATII cells (SV40-T2 cells) (18). HGF increases cell migration but not proliferation during human nasal epithelial repair in vitro (66).…”

Interleukin-1β and tumor necrosis factor-α have opposite effects on fibroblasts and epithelial cells during basement membrane formation

“…After 3 days of culture in DMEM with 10% FBS and 0.2 mM Asc-2P, fibroblasts embedded gel were co-cultured with SV40-T2 cells that were seeded on collagen fibrils in a cell culture insert in DMEM with 1% FBS and 0.2 mM Asc-2P in the presence of IL-1β and/ or TNF-α for 10 days. In another experiment, SV40-T2 cells were cultured on the basement membrane substratum in a cell culture insert that was prepared as described previously (Furuyama and Mochitate, 2004) in the presence of fibroblasts-embedded gel in DMEM with 1% FBS and 0.2 mM Asc-2P. For neutralizing the effect of TGF-βs, SV40-T2 cells were treated with 50 µg/ml anti-TGF-β1, 2, 3 antibody.…”