scholarly journals Extracellular signal-regulated kinase and Akt activation play a critical role in the process of hepatocyte growth factor-induced epithelial-mesenchymal transition

2012 ◽  
Vol 42 (2) ◽  
pp. 556-564 ◽  
Author(s):  
TOSHIYUKI TANAHASHI ◽  
SHINJI OSADA ◽  
ATSUKO YAMADA ◽  
JUNKO KATO ◽  
KAZUNORI YAWATA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition ◽  
Akt Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Hepatocyte Growth

scholarly journals Cbl-transforming Variants Trigger a Cascade of Molecular Alterations That Lead to Epithelial Mesenchymal Conversion

2000 ◽  
Vol 11 (10) ◽  
pp. 3397-3410 ◽  
Author(s):  
Tanya M. Fournier ◽  
Louie Lamorte ◽  
Christiane R. Maroun ◽  
Mark Lupher ◽  
Hamid Band ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Cell Spreading ◽  
Mesenchymal Transition ◽  
Amino Terminal ◽  
Src Homology ◽  
Hepatocyte Growth

Dispersal of epithelial cells is an important aspect of tumorigenesis, and invasion. Factors such as hepatocyte growth factor induce the breakdown of cell junctions and promote cell spreading and the dispersal of colonies of epithelial cells, providing a model system to investigate the biochemical signals that regulate these events. Multiple signaling proteins are phosphorylated in epithelial cells during hepatocyte growth factor–induced cell dispersal, including c-Cbl, a protooncogene docking protein with ubiquitin ligase activity. We have examined the role of c-Cbl and a transforming variant (70z-Cbl) in epithelial cell dispersal. We show that the expression of 70z-Cbl in Madin-Darby canine kidney epithelial cells resulted in the breakdown of cell–cell contacts and alterations in cell morphology characteristic of epithelial–mesenchymal transition. Structure–function studies revealed that the amino-terminal portion of c-Cbl, which corresponds to the Cbl phosphotyrosine-binding/Src homology domain 2 , is sufficient to promote the morphological changes in cell shape. Moreover, a point mutation at Gly-306 abrogates the ability of the Cbl Src homology domain 2 to induce these morphological changes. Our results identify a role for Cbl in the regulation of epithelial–mesenchymal transition, including loss of adherens junctions, cell spreading, and the initiation of cell dispersal.

scholarly journals Mesenchymal Stem Cells Attenuates TGF-β1-Induced EMT by Increasing HGF Expression in HK-2 Cells

2021 ◽  
Author(s):  
Jun-Jun Wei ◽  
Li Tang ◽  
Liang-Liang Chen ◽  
Zhen-Hua Xie ◽  
Yu Ren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth ◽  
Tgf Β1

Background: Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor beta 1 (TGF-β1)-induced epithelial mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-β1. Methods: Our study was performed at Ningbo University, Ningbo, Zhejiang, China between Mar 2017 and Jun 2018. HK-2 cells were initially treated with TGF-β1，then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTS assay and flow cytometry were employed to detect the effect of TGF-β1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 cells EMT. Results: Overexpressing TGF-β1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished. Conclusion: TGF-β1 was a motivating factor of kidney cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-β1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti- fibrosis.  

scholarly journals Sorafenib Inhibits the Hepatocyte Growth Factor–Mediated Epithelial Mesenchymal Transition in Hepatocellular Carcinoma

2011 ◽  
Vol 10 (1) ◽  
pp. 169-177 ◽  
Author(s):  
Tomoyuki Nagai ◽  
Tokuzo Arao ◽  
Kazuyuki Furuta ◽  
Kazuko Sakai ◽  
Kanae Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth

scholarly journals Hepatocyte Growth Factor Inhibits Apoptosis by the Profibrotic Factor Angiotensin II via Extracellular Signal-regulated Kinase 1/2 in Endothelial Cells and Tissue Explants

2010 ◽  
Vol 21 (23) ◽  
pp. 4240-4250 ◽  
Author(s):  
Young H. Lee ◽  
Ana P. Marquez ◽  
Ognoon Mungunsukh ◽  
Regina M. Day
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Caspase 3 ◽  
Cytoplasmic Localization ◽  
Ang Ii ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Induced Apoptosis ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF), an endogenous tissue repair factor, attenuates apoptosis in many primary cell types, but the mechanism is not completely understood. Our laboratory demonstrated that angiotensin (Ang) II activates the intrinsic apoptotic pathway in primary endothelial cells (ECs) via reduction of the antiapoptotic protein Bcl-xL. Ang II decreased Bcl-xLmRNA half-life by reducing its binding to nucleolin, a protein that normally binds a 3′ AU-rich region and stabilizes Bcl-xLmRNA. We hypothesized HGF may block apoptosis induced by Ang II. We used primary EC and ex vivo cultures of rat lung tissue to investigate HGF inhibition of Ang II-induced apoptosis. Our data indicated HGF abrogated Ang II-induced apoptosis by inhibiting cytochrome c release, caspase-3 activation, and DNA fragmentation. RNA-immunoprecipitation experiments demonstrated that HGF stabilized Bcl-xLmRNA by increasing nucleolin binding to the 3′-untranslated region that was associated with cytoplasmic localization of nucleolin. Cytoplasmic localization of nucleolin and Bcl-xLmRNA stabilization required HGF activation of extracellular signal-regulated kinase (ERK)1/2, but not phosphatidylinositol 3-kinase. HGF also blocked Ang II-induced caspase-3 activation and lactate dehydrogenase release in tissue explants in an ERK-dependent manner.

scholarly journals Activation of Cdc42, Rac, PAK, and Rho-Kinase in Response to Hepatocyte Growth Factor Differentially Regulates Epithelial Cell Colony Spreading and Dissociation

2000 ◽  
Vol 11 (5) ◽  
pp. 1709-1725 ◽  
Author(s):  
Isabelle Royal ◽  
Nathalie Lamarche-Vane ◽  
Louie Lamorte ◽  
Kozo Kaibuchi ◽  
Morag Park
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Rho Kinase ◽  
Cell Spreading ◽  
Dominant Negative ◽  
Phosphatidylinositol 3 Kinase ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF), the ligand for the Met receptor tyrosine kinase, is a potent modulator of epithelial–mesenchymal transition and dispersal of epithelial cells, processes that play crucial roles in tumor development, invasion, and metastasis. Little is known about the Met-dependent proximal signals that regulate these events. We show that HGF stimulation of epithelial cells leads to activation of the Rho GTPases, Cdc42 and Rac, concomitant with the formation of filopodia and lamellipodia. Notably, HGF-dependent activation of Rac but not Cdc42 is dependent on phosphatidylinositol 3-kinase. Moreover, HGF-induced lamellipodia formation and cell spreading require phosphatidylinositol 3-kinase and are inhibited by dominant negative Cdc42 or Rac. HGF induces activation of the Cdc42/Rac-regulated p21-activated kinase (PAK) and c-Jun N-terminal kinase, and translocation of Rac, PAK, and Rho-dependent Rho-kinase to membrane ruffles. Use of dominant negative and activated mutants reveals an essential role for PAK but not Rho-kinase in HGF-induced epithelial cell spreading, whereas Rho-kinase activity is required for the formation of focal adhesions and stress fibers in response to HGF. We conclude that PAK and Rho-kinase play opposing roles in epithelial–mesenchymal transition induced by HGF, and provide new insight regarding the role of Cdc42 in these events.

scholarly journals Involvement of Hepatocyte Growth Factor-Induced Epithelial-Mesenchymal Transition in Human Adenomyosis1

2015 ◽  
Vol 92 (2) ◽  
Author(s):  
Khaleque Newaz Khan ◽  
Michio Kitajima ◽  
Koichi Hiraki ◽  
Akira Fujishita ◽  
Masahiro Nakashima ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth

scholarly journals Activation of NF-κB Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis

2002 ◽  
Vol 22 (4) ◽  
pp. 1060-1072 ◽  
Author(s):  
Markus Müller ◽  
Alessandro Morotti ◽  
Carola Ponzetto
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Transcriptional Activation ◽  
Mitogen Activated Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Biological Responses ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Hepatocyte Growth

ABSTRACT Hepatocyte growth factor (HGF) and its receptor, Met, regulate a number of biological functions in epithelial and nonepithelial cells, such as survival, motility, proliferation, and tubular morphogenesis. The transcription factor NF-κB is activated in response to a wide variety of stimuli, including growth factors, and is involved in biological responses in part overlapping with those triggered by HGF. In this work we used the liver-derived MLP29 cell line to study the possible involvement of NF-κB in HGF/Met signaling. HGF stimulates NF-κB DNA binding and transcriptional activation via the canonical IκB phosphorylation-degradation cycle and via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase cascades. Phosphatidylinositol 3-kinase is not involved in Met-mediated NF-κB activation. Blockage of NF-κB activation in MLP29 cells by forced expression of the NF-κB super-repressor IκBα2A does not interfere with HGF-induced scatter but inhibits proliferation and tubulogenesis. Surprisingly, in the same cells NF-κB appears to be dispensable for the antiapoptotic function of HGF.

Diosgenin Suppresses Hepatocyte Growth Factor (HGF)-Induced Epithelial–Mesenchymal Transition by Down-regulation of Mdm2 and Vimentin

2011 ◽  
Vol 59 (10) ◽  
pp. 5357-5363 ◽  
Author(s):  
Hsiang-Yu Chang ◽  
Ming-Ching Kao ◽  
Tzong-Der Way ◽  
Chi-Tang Ho ◽  
Earl Fu
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth
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