scholarly journals Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC δ and E-cadherin

2007 ◽  
Vol 19 (11) ◽  
pp. 2329-2338 ◽  
Author(s):  
Yutong Zhao ◽  
Donghong He ◽  
Randi Stern ◽  
Peter V. Usatyuk ◽  
Ernst Wm. Spannhake ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Lysophosphatidic Acid ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Factor C ◽  
Hepatocyte Growth ◽  
E Cadherin

scholarly journals Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

2008 ◽  
Vol 294 (4) ◽  
pp. L778-L786 ◽  
Author(s):  
Young H. Lee ◽  
Yuichiro J. Suzuki ◽  
Autumn J. Griffin ◽  
Regina M. Day
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Gene Transcription ◽  
Bronchial Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Cox 2 ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) is upregulated in response to lung injury and has been implicated in tissue repair through its antiapoptotic and proliferative activities. Cyclooxygenase-2 (COX-2) is an inducible enzyme in the biosynthetic pathway of prostaglandins, and its activation has been shown to play a role in cell growth. Here, we report that HGF induces gene transcription of COX-2 in human bronchial epithelial cells (HBEpC). Treatment of HBEpC with HGF resulted in phosphorylation of the HGF receptor (c-Met), activation of Akt, and upregulation of COX-2 mRNA. Adenovirus-mediated gene transfer of a dominant negative (DN) Akt mutant revealed that HGF increased COX-2 mRNA in an Akt-dependent manner. COX-2 promoter analysis in luciferase reporter constructs showed that HGF regulation required the β-catenin-responsive T cell factor-4 binding element (TBE). The HGF activation of the COX-2 gene transcription was blocked by DN mutant of β-catenin or by inhibitors that blocked activation of Akt. Inhibition of p42/p44 MAPK pathway blocked HGF-mediated activation of β-catenin gene transcription but not Akt activation, suggesting that p42/p44 MAPK acts in a parallel mechanism for β-catenin activation. We also found that inhibition of COX-2 with NS-398 blocked HGF-induced growth in HBEpC. Together, the results show that the HGF increases COX-2 gene expression via an Akt-, MAPK-, and β-catenin-dependent pathway in HBEpC.

Stimulatory effects of hepatocyte growth factor on normal and neoplastic human bronchial epithelial cells

1995 ◽  
Vol 268 (6) ◽  
pp. L1012-L1020 ◽  
Author(s):  
P. Singh-Kaw ◽  
R. Zarnegar ◽  
J. M. Siegfried
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Western Blotting ◽  
Cell Types ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Brdu Labeling ◽  
Hepatocyte Growth

We examined the mitogenic, chemoinvasive, and chemotactic effects of hepatocyte growth factor (HGF) toward normal and neoplastic human epithelial cells derived from the bronchial mucosa. Primary cultures of human bronchial epithelial cells (HBE cells), immortalized bronchial epithelial cells (IB3-1 cells), and cells derived from a squamous cell carcinoma of the lung (128-88T cells) were used as targets. HGF was mitogenic for all three cell types as measured by bromodeoxyuridine (BrdU) labeling and colony-forming efficiency (CFE). With the use of BrdU labeling, 9.8-16.8% of nuclei were labeled in controls vs. 56.9-65.6% labeled nuclei in cells treated with HGF. HGF stimulated colony formation 3.6-6.2-fold over untreated control. Analysis by reverse transcription-polymerase chain reaction demonstrated the presence of the c-met gene, the receptor for HGF, in all three cell types. Cell lysates from all three cell types contained proteins that were recognized by a c-met antibody as determined by Western blotting. The gene for HGF was not expressed in any of the cell types, although it was expressed in control MRC5 fibroblasts. No HGF protein could be detected by Western blotting in the conditioned medium from epithelial cells, although it was readily detectable in medium conditioned by lung fibroblasts. HGF proved to be a powerful chemotactic agent for all three cell types and also stimulated invasion into Matrigel, an artificial basement membrane. The results indicate HGF acts mainly as a paracrine growth factor for cells derived from the human bronchus, and may play a role in the growth and progression of lung tumors.

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