scholarly journals Hepatocyte Growth Factor Overexpression Slows the Progression of 4NQO-Induced Oral Tumorigenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoxi He ◽  
Si Chen ◽  
Yinghua Tang ◽  
Xiaomin Zhao ◽  
Liting Yan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Enrichment Analysis ◽  
Akt Signaling ◽  
Clinicopathological Parameters ◽  
Epithelial Tissue ◽  
Rna Seq ◽  
Highly Correlated ◽  
Oral Epithelial ◽  
Hepatocyte Growth

ObjectivesTo investigate the role of hepatocyte growth factor (HGF)/c-Met signaling in oral malignant transformation.MethodsWe used immunohistochemistry to investigate HGF and c-Met expression in 53 oral squamous cell carcinoma (OSCC) specimens and 21 adjacent nontumor specimens and evaluated the associations between HGF and c-Met expression and clinicopathological parameters. Additionally, HGF-overexpression transgenic (HGF-Tg) and wild-type (Wt) mice were treated with 4-nitroquinoline-1-oxide (4NQO) to induce oral carcinogenesis for 16 weeks. At 16, 20, and 24 weeks, tongue lesions were collected for clinical observation; estimation of HGF, c-Met, and PCNA expression; apoptosis (TUNEL) assays; and RNA sequencing (RNA-seq).ResultsHGF and c-Met were positively expressed in 92.5% and 64% of OSCC samples, respectively. High HGF expression was significantly associated with smaller tumor size (p = 0.006) and inferior TNM stage (p = 0.032). No correlation between HGF and c-Met levels and other clinical parameters or prognosis was noted. In addition, HGF and c-Met expression was elevated in 4NQO-induced lesions of Wt mice. Compared with Wt mice, HGF-Tg mice have lower tumor incidence, number, volume, and lesion grade. In addition, the percentage of PCNA-positive cells in Wt mice was significantly higher than that in HGF-Tg mice at different time points. At 16 weeks, HGF-Tg mice exhibited less apoptotic cells compared with Wt mice (p < 0.000), and these levels gradually increased until the levels were greater than that of Wt mice at 24 weeks (p < 0.000). RNA-seq data revealed that 140 genes were upregulated and 137 genes were downregulated in HGF-Tg mice. KEGG enrichment analysis showed that upregulated differentially expressed genes (DEGs) are highly correlated with oxidative and metabolic signaling and that downregulated DEGs are related to MAPK and PI3K-AKT signaling.ConclusionsHGF and c-Met expression is upregulated in OSCC tissues and is associated with the occurrence and development of OSCC. HGF overexpression in normal oral epithelial tissue can inhibit 4NQO-induced tumorigenesis potentially through inhibiting proliferation and accelerating apoptosis via MAPK and PI3K-AKT signaling.

scholarly journals Effect of FGF-21 on implant bone defects through hepatocyte growth factor (HGF)-mediated PI3K/AKT signaling pathway

2019 ◽  
Vol 109 ◽  
pp. 1259-1267 ◽  
Author(s):  
Shimao Yang ◽  
Yanwei Guo ◽  
Wenmei Zhang ◽  
Jin Zhang ◽  
Yujie Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Bone Defects ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Hepatocyte Growth

scholarly journals A minimal hepatocyte growth factor mimic acting as a powerful agonist of the MET receptor tyrosine kinase for regeneration of epithelial tissues and organs

2020 ◽  
Author(s):  
Bérénice Leclercq ◽  
Giovanni de Nola ◽  
Alexandra Mougel ◽  
Solenne Dezitter-Tarron ◽  
Claire Simonneau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Epithelial Tissue ◽  
Met Receptor ◽  
Met Receptor Tyrosine Kinase ◽  
Wide Range ◽  
Hepatocyte Growth

AbstractDegenerative diseases of major internal epithelial organs such as liver, lung and kidney account for more than one third of mortality worldwide. The huge demand for drugs able to limit epithelial tissue degradation and eventually restore its functionality, place mimics of the hepatocyte growth factor/scatter factor (HGF/SF), the physiological ligand for the MET receptor tyrosine kinase, at the forefront of potential drug candidates. HGF/SF is a growth and motility factor with essential physiological roles in development and regeneration of epithelial organs. Unfortunately, HGF/SF itself is unsuitable for therapy because naturally the factor acts only locally as a morphogen and chemoattractant and has poor in vivo distribution and shelf life profile. We have therefore designed, produced, solved the crystal structure and characterized the biochemical and biological properties of K1K1, a new engineered fragment of HGF/SF for applications in tissue/organ regeneration. K1K1, a covalent dimer of the first kringle domain of HGF/SF, is recombinantly produced in bacterial cells, shows superior stability at physiological pH and ionic strength and is a potent receptor agonist as demonstrated in a wide range of biological assays with cells in culture and initial in vivo studies. K1K1 has broad potential in regenerative medicine with diseases such as acute liver failure, non-alcoholic steatohepatitis, chronic obstructive pulmonary disease and acute kidney injury.

Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway

2003 ◽  
Vol 309 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Jun-ichi Okano ◽  
Goshi Shiota ◽  
Kazuya Matsumoto ◽  
Sakiko Yasui ◽  
Akihiro Kurimasa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Oval Cells ◽  
Akt Signaling Pathway ◽  
Proliferative Effect ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1315-1324 ◽  
Author(s):  
H. Ohmichi ◽  
U. Koshimizu ◽  
K. Matsumoto ◽  
T. Nakamura
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Lung Development ◽  
Keratinocyte Growth Factor ◽  
Receptor Gene ◽  
Neutralizing Antibody ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
Epithelial Tissue ◽  
Hepatocyte Growth

Mesenchymal-epithelial tissue interactions are important for development of various organs, and in many cases, soluble signaling molecules may be involved in this interaction. Hepatocyte growth factor (HGF) is a mesenchyme-derived factor which has mitogenic, motogenic and morphogenic activities on various types of epithelial cells and is considered to be a possible mediator of epithelial-mesenchymal interaction during organogenesis and organ regeneration. In this study, we examined the role of HGF during lung development. In situ hybridization analysis showed HGF and the c-met/HGF receptor gene to be respectively expressed in mesenchyme and epithelium in the developing lung. In organ cultures, exogenously added HGF apparently stimulated branching morphogenesis of the fetal lung. In contrast, HGF translation arrest or neutralization assays resulted in clear inhibition of epithelial branching. These results suggest that HGF is a putative candidate for a mesenchyme-derived morphogen regulating lung organogenesis. We also found that HGF is involved in epithelial branching, in collaboration with fibroblast growth factor (FGF) family molecule(s). In mesenchyme-free culture, HGF alone did not induce epithelial morphogenesis, however, addition of both HGF and acidic FGF (aFGF) or keratinocyte growth factor (KGF), ligands for the KGF receptor, induced epithelial branching more extensively than that was observed in explants treated with aFGF or KGF alone. In addition, the simultaneous inhibition of HGF- and FGF-mediated signaling using neutralizing antibody and antisense oligo-DNA resulted in drastic impairment of epithelial growth and branching. Possible interactions between HGF and FGFs or other growth factors in lung development is given consideration.

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