Fetal Growth Factors*
Emilio Herrera, Robert H. Knopp in Perinatal Biochemistry, 2020
Hepatocyte growth factor (HGF) was first purified from the serum of patients with fulminant hepatic failure. HGF from this source displayed a potency for stimulation of hepatocyte growth which was one order of magnitude greater than that of EGF. HGF expression has been shown to increase during liver regeneration in response to experimental liver injury or partial hepatectomy in the rat.50 Bottaro et al.51 recently showed that the HGF receptor is the c-met proto-oncogene product, a previously characterized tyrosine kinase. Thus, the mitogenic actions of HGF may be transduced via a pathway similar to those for insulin, EGF or the IGFs. While the involvement of HGF in fetal hepatic growth has not yet been established, its relative specificity places it in a position of potential importance.
Islet Transplantation in Type 1 Diabetes: Stem Cell Research and Therapy
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
Evidences exist which show that hepatocyte growth factor (HGF) which is a mesenchymal factor which induces β-cell formation. Another mesenchymal factor epidermal growth factor (EGF) regulates the proliferation of developing pancreas. Some glucagon family members such as glucagon-like peptide 1 and 2 (GLP-1 and GLP-2), glucose insulinotrophic peptide (GIP) play a role in early differentiation of insulin-producing cells [39]. GLP-1 signaling enhances the proliferation of existing cells, induces islet neogenesis and inhibits β-cell apoptosis [40, 41]. GIP promotes growth and survival of pancreatic β-cells by increasing expression of Bcl-2 (anti-apoptotic gene) and decreasing the pro-apoptotic gene Bax which results in diminished β-cell death [42]. Both GIP and GLP-1 are primary physiological incretins which are intestinal hormones that are released in response to ingested food and stimulate insulin secretion in glucose-dependent manner [43].
The Molecular Genetics and Pathology of Renal Cell Carcinoma
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
c-MET acts as a cell-surface receptor for the hepatocyte growth factor/scatter factor (HGF/SF), and normally is involved in diverse biological events such as cell growth, migration and morphogenesis. Upon stimulation by HGF/SF, the c-MET receptor kinase undergoes autophosphorlyation on multiple tyrosine residues and recruits a number of signal transducers and adapter proteins to its cytoplasmic domain and multiple docking sites (such as growth factor receptor-bound protein 2 (Grb2), Gab1, phosphatidylinositol 3-kinase (PI3K), phospholipase C-γ, Shc and Src) (103). This results in the activation of several downstream signaling pathways resulting in pleotropic effects. For example, the direct binding of Grb2 to c-MET activates the Ras/mitogen-activated pathway regulating cell-cycle progression (103) and Gab1 is involved in initiating morphogenesis, cell motility and apoptosis (104).
Effects of hepatocyte growth factor-transfected mesenchymal stem cell transplantation in canine injured vocal folds
Published in Growth Factors, 2023
Xingqiao Xie, Xumao Li, Xinsheng Lin, Xiangyu Chen, Chenshan Zhang, Guangbin Sun
Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays an important role in embryogenesis, organogenesis, and tissue regeneration (Kumai 2019). HGF exerts antifibrotic properties by promoting matrix metalloproteinase-1 (MMP-1) secreted by fibroblasts and inhibiting the expression of transforming growth factor β1 (TGF-β1), thus increasing the synthesis of hyaluronic acid (HA) and reducing the production of type I collagen. However, the effects of HGF cannot be sustained over a long duration due to its short half-life (Xu and Fan 2021). However, in its genetic form coupled with a recombinant lentivirus transfected into ADSCs, the biological effects of HGF can be sustained over a long period (Martínez-Molina et al. 2020). Therefore, HGF-transfected ADSCs may exert sustained beneficial effects compared to growth factor therapy or stem cell therapy alone (Zhu et al. 2013). Thus, this study aimed to investigate the efficacy of HGF-transfected ADSCs by evaluating the morphological and histological changes of injured canine VFs.
Reviving the role of MET in liver cancer therapy and vaccination: an autophagic perspective
Published in OncoImmunology, 2020
Xing Huang, Gang Zhang, Xueli Bai, Tingbo Liang
As the tissue with the greatest regenerative potential, liver naturally has a few phenotypes very similar to those of tumors, including self-sufficiency in growth signals and limitless replicative potential. The hepatocyte growth factor (HGF) and its receptor MET were identified decades ago and initially found to be closely related to liver regeneration. Subsequent studies confirmed their abnormal expression and sustained activation in a variety of malignant tumors including liver cancer. As an important member of the receptor tyrosine kinase (RTK) family, MET dimerizes upon binding HGF, and then auto-phosphorylates to activate phosphoinositide-3-kinase (PI3K)–protein kinase B (AKT) and other downstream signaling pathways that promote cell proliferation and epithelial-mesenchymal transformation. It has been reported that the HGF-MET signaling pathway regulates multiple aspects of cancer, including its occurrence and development, invasion and metastasis, and therapeutic resistance.1 As a result, there was early development of HGF/MET-targeted drug candidates, such as monoclonal antibodies against the extracellular binding sites of receptors as well as small molecular inhibitors that directly target the intracellular kinase activity center.2,3 Unfortunately, previous attempts to put these drugs into clinical practice failed or were put on hold. Why was targeted therapy against such important targets ineffective? We surmise that the current understanding of the action mechanism of the HGF-MET signaling pathway in liver cancer, especially in mediating drug resistance, is not sufficiently comprehensive.
Hepatocyte growth factor levels in livers and serum at Kasai-portoenterostomy are not predictive of clinical outcome in infants with biliary atresia
Published in Growth Factors, 2019
Omid Madadi-Sanjani, Joachim F. Kuebler, Stephanie Dippel, Anna Gigina, Christine S. Falk, Gertrud Vieten, Claus Petersen, Christian Klemann
Growth factors are known to play an important role in regenerative processes after liver injury and thus might have a protective role during the development of BA-associated liver cirrhosis. Hepatocyte growth factor (HGF) is secreted by mesenchymal cells and functions as pleiotropic cytokine mostly on epithelial cells (Ricci, Catizone, and Galdieri 2002). HGF stimulates cell division and motility and thus has a pivotal role in angiogenesis, tumor-genesis, and liver tissue regeneration (Spix et al. 2007; Tao et al. 2017). In liver diseases such as in hepatocellular carcinoma or in pediatric liver tumors like hepatoblastoma serum levels have shown to be increased (von Schweinitz et al. 1998; Tsunoda et al. 1998; von Schweinitz et al. 2000; Karabulut et al. 2014). Likewise, it’s been known for more than 30 years that serum levels of HGF in children with BA are increased in comparison with healthy controls (Tsau et al. 1997). However, the possible clinical value of HGF levels in sera and also within the liver to predict the further course of BA remains elusive. Therefore, we assessed HGF as a marker of liver regeneration and fibrosis at the time point of KPE in infants with BA in sera and liver and performed correlation studies regarding age, bilirubin, and ISHAK-score at KPE and most importantly the further course of disease. In addition, we included Interleukin 6 (IL-6) in sera and liver tissue as a marker of inflammation possibly influencing HGF levels.
Related Knowledge Centers
- Epithelium
- Haematopoiesis
- Morphogenesis
- Paracrine Signaling
- Endothelium
- Myogenesis
- Mesenchymal Stem Cell
- Motility
- T Cell
- Tyrosine Kinase