Has HGF met other partners? Met-independent epithelial morphogenesis induced by HGF. Focus on “Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity”

2004 ◽  
Vol 286 (3) ◽  
pp. C475-C477 ◽  
Author(s):  
Prasad Devarajan
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tight Junction ◽  
Mdck Cell ◽  
Epithelial Morphogenesis ◽  
Cell Morphogenesis ◽  
Functional Integrity ◽  
Hepatocyte Growth

Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity

2004 ◽  
Vol 286 (3) ◽  
pp. C482-C494 ◽  
Author(s):  
Anne L. Pollack ◽  
Gerard Apodaca ◽  
Keith E. Mostov
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tight Junction ◽  
Mdck Cell ◽  
Mdck Cells ◽  
Peak Effect ◽  
Ruthenium Red ◽  
Functional Integrity ◽  
Organ Regeneration ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) induces mitogenesis, motogenesis, and tubulogenesis of cultured Madin-Darby canine kidney (MDCK) epithelial cells. We report that in addition to these effects HGF stimulates morphogenesis of tight, polarized MDCK cell monolayers into pseudostratified layers without loss of tight junction (TJ) functional integrity. We tested TJ functional integrity during formation of pseudostratified layers. In response to HGF, the TJ marker ZO-1 remained in morphologically complete rings and functional barriers to paracellular diffusion of ruthenium red were maintained in pseudostratified layers. Transepithelial resistance (TER) increased transiently two- to threefold during the morphogenetic transition from monolayers to pseudostratified layers and then declined to baseline levels once pseudostratified layers were formed. In MDCK cells expressing the trk/met chimera, both HGF and NGF at concentrations of 2.5 ng/ml induced scattering. However, 2.5 ng/ml HGF did not affect TER. The peak effect of HGF on TER was at a concentration of 100 ng/ml. In contrast, NGF at concentrations as high as 25 μg/ml had no effect on TER or pseudostratified layer morphogenesis of trk/met-expressing cultures. These results suggest that altered presentation of the stimulus, such as through HGF interaction with low-affinity sites, may change the downstream signaling response. In addition, our results demonstrate that HGF stimulates pseudostratified layer morphogenesis while inducing an increase in TER and maintaining the overall tightness of the epithelial layer. Stimulation of epithelial cell movements by HGF without loss of functional TJs may be important for maintaining epithelial integrity during morphogenetic events such as formation of pseudostratified epithelia, organ regeneration, and tissue repair.

scholarly journals HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion

2005 ◽  
Vol 16 (2) ◽  
pp. 550-561 ◽  
Author(s):  
Hanane Khoury ◽  
Monica A. Naujokas ◽  
Dongmei Zuo ◽  
Veena Sangwan ◽  
Melanie M. Frigault ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Invasion ◽  
Single Cells ◽  
Epithelial Morphogenesis ◽  
Cell Junctions ◽  
Junction Protein ◽  
Hepatocyte Growth ◽  
E Cadherin ◽  
Cell Cell

Activation of the hepatocyte growth factor receptor Met induces a morphogenic response and stimulates the formation of branching tubules by Madin-Darby canine kidney (MDCK) epithelial cells in three-dimensional cultures. A constitutively activated ErbB2/Neu receptor, NeuNT, promotes a similar invasive morphogenic program in MDCK cells. Because both receptors are expressed in breast epithelia, are associated with poor prognosis, and hepatocyte growth factor (HGF) is expressed in stroma, we examined the consequence of cooperation between these signals. We show that HGF disrupts NeuNT-induced epithelial morphogenesis, stimulating the breakdown of cell-cell junctions, dispersal, and invasion of single cells. This correlates with a decrease in junctional proteins claudin-1 and E-cadherin, in addition to the internalization of the tight junction protein ZO-1. HGF-induced invasion of NT-expressing cells is abrogated by pretreatment with a pharmacological inhibitor of the mitogen-activated protein kinase kinase (MEK) pathway, which restores E-cadherin and ZO-1 at cell-cell junctions, establishing the involvement of MEK-dependent pathways in this process. These results demonstrate that physiological signals downstream from the HGF/Met receptor synergize with ErbB2/Neu to enhance the malignant phenotype, promoting the breakdown of cell-cell junctions and enhanced cell invasion. This is particularly important for cancers where ErbB2/Neu is overexpressed and HGF is a physiological growth factor found in the stroma.

scholarly journals Hepatocyte Growth Factor stimulated cell scattering requires ERK and Cdc42-dependent tight junction disassembly

2010 ◽  
Vol 400 (2) ◽  
pp. 271-277 ◽  
Author(s):  
Akashi Togawa ◽  
Jeffery Sfakianos ◽  
Shuta Ishibe ◽  
Sayuri Suzuki ◽  
Yoshihide Fujigaki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tight Junction ◽  
Cell Scattering ◽  
Hepatocyte Growth

scholarly journals Hepatocyte Growth Factor Alters Renal Epithelial Cell Susceptibility to Uropathogenic Escherichia coli

2001 ◽  
Vol 12 (12) ◽  
pp. 2543-2553
Author(s):  
John H. Wu ◽  
Barry J. Billings ◽  
Daniel F. Balkovetz
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Hepatocyte Growth Factor ◽  
Cell Polarity ◽  
Mdck Cell ◽  
Cell Monolayers ◽  
Hepatocyte Growth

ABSTRACT. The urinary tract is frequently the source of Escherichia coli bacteremia. Bacteria from the urinary tract must cross an epithelial layer to enter the bloodstream. Hepatocyte growth factor (HGF) alters the polarity of Madin-Darby canine kidney (MDCK) epithelial cells. The role of cell polarity in determining renal epithelial resistance to Escherichia coli invasion is not well known. A model of polarized and HGF-treated MDCK epithelial cells grown on filters was used to study the role of epithelial cell polarity during the interaction of nonvirulent (XL1-Blue) and uropathogenic (J96) strains of Escherichia coli with renal epithelium. Basolateral exposure of MDCK cells to J96, but not XL1-Blue, resulted in loss of transepithelial resistance (TER), which was due to epithelial cytotoxicity and not degradation of epithelial junctional proteins by bacterial proteases. Apical exposure to both J96 and XL1-Blue did not alter TER. Pretreatment of polarized MDCK cell monolayers with HGF renders the cells sensitive to loss of TER and cytotoxicity by apical exposure to J96. Analysis by confocal microscopy demonstrated that HGF treatment of MDCK cell monolayers also greatly enhances adherence of J96 to the apical surface of the cell monolayer. These data demonstrate that the basolateral surface of polarized epithelia is more susceptible to J96 cytotoxicity. The data also support the hypothesis that processes that alter epithelial cell polarity increase sensitivity of epithelia to bacterial injury and adherence from the apical compartment.

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