Hepatocyte growth factor in physiology and infectious diseases

Abstract

Hepatocyte growth factor (HGF) is a pleiotropic cytokine composed of an α-chain and a β-chain, and these chains contain four kringle domains and a serine protease-like structure, respectively. The receptor for HGF was identified as the c-met proto-oncogene product of transmembrane receptor tyrosine kinase. HGF-induced signaling through the receptor Met provokes dynamic biological responses that support morphogenesis, regeneration, and the survival of various cells and tissues, which includes hepatocytes, renal tubular cells, and neurons. Characterization of tissue-specific Met knockout mice has further indicated that the HGF-Met system modulates immune cell functions and also plays an inhibitory role in the progression of chronic inflammation and fibrosis. However, the biological actions that are driven by the HGF-Met pathway all play a role in the acquisition of the malignant characteristics in tumor cells, such as invasion, metastasis, and drug resistance in the tumor microenvironment. Even though oncogenic Met signaling remains the major research focus, the HGF-Met axis has also been implicated in infectious diseases. Many pathogens try to utilize host HGF-Met system to establish comfortable environment for infection. Their strategies are not only simply change the expression level of HGF or Met, but also actively hijack HGF-Met system and deregulating Met signaling using their pathogenic factors. Consequently, the monitoring of HGF and Met expression, along with real-time detection of Met activation, can be a beneficial biomarker of these infectious diseases. Preclinical studies designed to address the therapeutic significance of HGF have been performed on injury/disease models, including acute tissue injury, chronic fibrosis, and cardiovascular and neurodegenerative diseases. Likewise, manipulating the HGF-Met system with complete control will lead to a tailor made treatment for those infectious diseases.

Cellular signaling and gene expression profiles evoked by a bivalent macrocyclic peptide that serves as an artificial MET receptor agonist

“…Tissue-specific disruption of the MET receptor revealed indispensable or important roles for the HGF-MET receptor pathway in the regeneration and protection of tissues, including the liver, kidney, skin, nervous system tissue, pancreas, etc 12 . Administration of HGF is a therapeutic option in preclinical disease models, including models of fulminant hepatitis, liver cirrhosis, amyotrophic lateral sclerosis, and spinal cord injury 11 .…”

“…The MET receptor is a specific receptor for hepatocyte growth factor (HGF) 9 , 10 . Disruption of the gene encoding the MET receptor and therapeutic approaches with HGF have provided much evidence showing that MET receptor activation plays a definitive role in development, wound healing, regeneration, and anti-fibrosis 11 , 12 .…”

Marburg and Ebola virus infections elicit a complex, muted inflammatory state in bats

“…These included TFAM, OPA1, MFN1/2, and DNM1L. Two genes involved in mitochondrial biogenesis 46 , HGF-MET and PPARGC1A, are also upregulated upon MARV infection.…”

Hepatocyte growth factor protects PC12 cells against OGD/R-induced injury by reducing iron

“…Hepatocyte growth factor (HGF) is a pleiotropic cytokine [1,2]. The binding of HGF to its unique tyrosine kinase receptor, c-Met, induces activation of Met tyrosine kinase and the autophosphorylation of tyrosine residues in Met [3,4]. The activation of c-Met recruits adaptor molecules and activates several intracellular signaling pathways, and the signaling cascade results in specific cellular programs such as promoting angiogenesis, inhibiting fibrosis and apoptosis, regulating inflammation, and stimulating tissue regeneration [5,6].…”