Details for: HGF

Gene ID: 3082

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HGF

Ensembl ID: ENSG00000019991

Description: hepatocyte growth factor

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatic stellate cell CL0000632
    CSI 31
    rCSI 100%
    PRS 78.33
  • perivascular cell CL4033054
    CSI 22.47
    rCSI 30.71%
    PRS 88.77
  • fibroblast of lung CL0002553
    CSI 8.31
    rCSI 7.73%
    PRS 85.77
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.32
    rCSI 2.55%
    PRS 88.13
  • Mueller cell CL0000636
    CSI 3.28
    rCSI 7.49%
    PRS 77.04
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.24
    rCSI 3.55%
    PRS 86.49
  • alternatively activated macrophage CL0000890
    CSI 2.87
    rCSI 3.61%
    PRS 92.22
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.81
    rCSI 8.14%
    PRS 83.92
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.69
    rCSI 3.47%
    PRS 69.86
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.38
    rCSI 6.21%
    PRS 85.98
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.29
    rCSI 2.85%
    PRS 66.58
  • vascular associated smooth muscle cell CL0000359
    CSI 2.28
    rCSI 7.38%
    PRS 82.92
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.23
    rCSI 3.56%
    PRS 88.02
  • lung pericyte CL0009089
    CSI 2.18
    rCSI 5.76%
    PRS 90.03
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.08
    rCSI 1.8%
    PRS 88.06
  • promonocyte CL0000559
    CSI 2.06
    rCSI 3.53%
    PRS 89.21
  • renal interstitial pericyte CL1001318
    CSI 1.99
    rCSI 5.48%
    PRS 80.73
  • lung neuroendocrine cell CL1000223
    CSI 1.84
    rCSI 2.72%
    PRS 87.67
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.77
    rCSI 3.97%
    PRS 69.53
  • common myeloid progenitor CL0000049
    CSI 1.75
    rCSI 1.42%
    PRS 86.94
  • common dendritic progenitor CL0001029
    CSI 1.64
    rCSI 2.05%
    PRS 91.61
  • Hofbauer cell CL3000001
    CSI 1.44
    rCSI 2.72%
    PRS 91.29
  • promyelocyte CL0000836
    CSI 1.42
    rCSI 2.04%
    PRS 89.15
  • alveolar adventitial fibroblast CL4028006
    CSI 1.36
    rCSI 2.15%
    PRS 85.96
  • pancreatic stellate cell CL0002410
    CSI 1.33
    rCSI 7.72%
    PRS 87.4
  • blood vessel smooth muscle cell CL0019018
    CSI 1.23
    rCSI 10.03%
    PRS 80.07
  • fibroblast of breast CL4006000
    CSI 1.05
    rCSI 4.41%
    PRS 88.01
  • smooth muscle cell of prostate CL1000487
    CSI 0.94
    rCSI 5.54%
    PRS 89.13
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.73
    rCSI 3.77%
    PRS 95.4
  • mesenchymal stem cell CL0000134
    CSI 0.14
    rCSI 1.57%
    PRS 88.51

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Hepatocyte Growth Factor, encoded by the [HGF](/details-gene/3082) gene, is a potent pleiotropic cytokine and morphogen. It functions as a secreted ligand for the MET proto-oncogene receptor tyrosine kinase, playing a critical role in cell proliferation, motility, morphogenesis, and tissue regeneration. The expression profile of [HGF](/details-gene/3082) indicates it is primarily produced by cells of mesenchymal origin. **Overall**, its significance is highest in [hepatic stellate cell](/details-cell/CL0000632), [perivascular cell](/details-cell/CL4033054), and [fibroblast of lung](/details-cell/CL0002553), highlighting its function as a paracrine signaling molecule that orchestrates complex biological programs such as wound healing, angiogenesis, and embryogenesis. Dysregulation of the HGF/MET signaling axis is implicated in tumorigenesis and metastatic progression, making it a key focus in cancer biology ([142409](https://omim.org/entry/142409)). ## Cellular Roles and Expression Landscape The expression landscape of [HGF](/details-gene/3082) underscores its primary role as a secreted factor produced by stromal and select immune cell populations to influence surrounding epithelial and endothelial cells. **Overall**, the gene's most significant expression is observed in mesenchymal and stromal cell types. It is a defining marker for [hepatic stellate cell](/details-cell/CL0000632) (CSI: 31.00), which are key players in liver homeostasis and fibrosis. High significance is also noted in other structural and perivascular cells, including [perivascular cell](/details-cell/CL4033054) (CSI: 22.47), [fibroblast of lung](/details-cell/CL0002553) (CSI: 8.31), [vascular associated smooth muscle cell](/details-cell/CL0000359) (CSI: 2.28), and [lung pericyte](/details-cell/CL0009089) (CSI: 2.18). This expression pattern is consistent with HGF's role in tissue maintenance, repair, and angiogenesis, where these cells secrete HGF to stimulate nearby target cells. In addition to its stromal expression, [HGF](/details-gene/3082) shows notable significance in specific myeloid cell subsets. These include [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 3.32) and [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 2.87), suggesting a role in modulating immune responses and orchestrating tissue remodeling during inflammation and its resolution. The expression by these cells suggests [HGF](/details-gene/3082) acts as a link between the immune system and tissue repair processes. ## Pathways and Molecular Function [HGF](/details-gene/3082) functions as a secreted protein with [growth factor activity](/details-go/GO:0008083) and [serine-type endopeptidase activity](/details-go/GO:0004252). Its primary mechanism of action is through binding to and activating the MET receptor, initiating the [Hepatocyte growth factor receptor signaling pathway](/details-go/GO:0048012). This activation triggers a cascade of intracellular signaling events that are central to its diverse biological effects. The downstream pathways regulated by HGF are extensive, as detailed in Reactome. Key among these are the activation of pro-survival and proliferative pathways such as [PI3K/Akt signaling in cancer](/details-reactome/R-HSA-2219528) and the [Raf/map kinase cascade](/details-reactome/R-HSA-5673001). These pathways are consistent with HGF's role in promoting [mitotic cell cycle](/details-go/GO:0000278) progression and providing a strong [negative regulation of apoptotic process](/details-go/GO:0043066). Furthermore, HGF is a potent regulator of cell motility and invasion. This is reflected in its involvement in processes like [positive regulation of cell migration](/details-go/GO:0030335), [cell chemotaxis](/details-go/GO:0060326), and [Epithelial to mesenchymal transition](/details-go/GO:0001837). These functions are mediated by pathways such as [Met promotes cell motility](/details-reactome/R-HSA-8875878). Its role within the immune system is highlighted by its involvement in [Cytokine signaling in immune system](/details-reactome/R-HSA-1280215) and its ability to modulate cytokine production, such as the [positive regulation of interleukin-10 production](/details-go/GO:0032733). This molecular signature solidifies the role of [HGF](/details-gene/3082) as a master regulator of cellular behavior in development, tissue homeostasis, and disease. ## Research Directions The central role of the HGF/MET axis in both physiological tissue repair and pathological states like cancer and fibrosis presents multiple avenues for investigation. The specific expression of [HGF](/details-gene/3082) by stromal cells makes it a critical mediator of the tissue microenvironment. **Proposed Hypotheses:** 1. Given its high expression in [hepatic stellate cell](/details-cell/CL0000632) and its function in liver regeneration, aberrant autocrine or paracrine HGF signaling within this cell population may be a critical switch that drives the transition from regenerative response to pathological fibrosis following chronic liver injury. 2. The expression of [HGF](/details-gene/3082) by [alternatively activated macrophage](/details-cell/CL0000890) suggests that macrophage-derived HGF is a key signal for promoting epithelial repair and angiogenesis during the resolution phase of inflammation, and its dysregulation could lead to chronic inflammatory conditions or impaired wound healing. **Experimental Approach:** To test the second hypothesis regarding the role of macrophage-derived HGF, one could utilize a conditional knockout mouse model. A mouse line with *Hgf* floxed alleles could be crossed with a LysM-Cre line to specifically delete [HGF](/details-gene/3082) in the myeloid lineage, including macrophages. These mice could then be subjected to a model of tissue injury, such as a skin wound healing model or a lung injury model (e.g., bleomycin-induced fibrosis). The healing process, re-epithelialization rate, angiogenesis, and inflammatory infiltrate could be compared between the conditional knockout and control mice using histology, immunohistochemistry, and flow cytometry. Furthermore, primary macrophages could be isolated from both mouse lines to directly assess their ability to promote epithelial cell migration and proliferation in a co-culture system. **Therapeutic Potential:** The HGF/MET pathway is a well-established therapeutic target with a dual nature. * **Inhibition:** In oncology, where the HGF/MET axis is frequently overactive and drives tumor growth, invasion, and resistance to therapy, [HGF](/details-gene/3082) represents a prime target for inhibition. Strategies include monoclonal antibodies that sequester [HGF](/details-gene/3082) (e.g., rilotumumab) or small molecule inhibitors that block the kinase activity of its receptor, MET (e.g., crizotinib, cabozantinib). These approaches are particularly relevant for cancers with MET amplification or mutations. * **Activation:** Conversely, in the context of regenerative medicine, the potent pro-survival and mitogenic properties of [HGF](/details-gene/3082) make it an attractive candidate for therapeutic activation. Recombinant HGF protein or gene therapy vectors expressing [HGF](/details-gene/3082) are being explored for treating conditions characterized by tissue damage and cell loss, such as acute liver failure, myocardial infarction, and peripheral artery disease.

Genular Protein ID: 2927579749

Symbol: HGF_HUMAN

Name: Hepatocyte growth factor

UniProtKB Accession Codes:

P14210 A1L3U6 Q02935 Q13494 Q14519 Q3KRB2 Q8TCE2 Q9BYL9 Q9BYM0 Q9UDU6

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 3 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 6 EMBL 36 Ensembl 5 EvolutionaryTrace 1 ExpressionAtlas 1 GO 36 Gene3D 3 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 35 PDBsum 35 PIR 1 PIRSF 2 PRINTS 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 6 RNAct 1 Reactome 18 RefSeq 9 SASBDB 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2528952

Title: Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor.

PubMed ID: 2528952

DOI: 10.1016/0006-291x(89)92316-4

PubMed ID: 2531289

Title: Molecular cloning and expression of human hepatocyte growth factor.

PubMed ID: 2531289

DOI: 10.1038/342440a0

PubMed ID: 2145836

Title: Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte.

PubMed ID: 2145836

DOI: 10.1016/s0006-291x(05)80212-8

PubMed ID: 1831432

Title: Organization of the human hepatocyte growth factor-encoding gene.

PubMed ID: 1831432

DOI: 10.1016/0378-1119(91)90080-u

PubMed ID: 1826653

Title: An alternatively processed mRNA generated from human hepatocyte growth factor gene.

PubMed ID: 1826653

DOI: 10.1111/j.1432-1033.1991.tb15876.x

PubMed ID: 1824873

Title: A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor.

PubMed ID: 1824873

DOI: 10.1073/pnas.88.2.415

PubMed ID: 1831266

Title: Evidence for the identity of human scatter factor and human hepatocyte growth factor.

PubMed ID: 1831266

DOI: 10.1073/pnas.88.16.7001

PubMed ID: 1720571

Title: Identification of a competitive HGF antagonist encoded by an alternative transcript.

PubMed ID: 1720571

DOI: 10.1126/science.1720571

PubMed ID: 1280830

Title: A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.

PubMed ID: 1280830

DOI: 10.1073/pnas.89.23.11574

PubMed ID: 8662798

Title: Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF/scatter factor variant with partial agonist/antagonist activity.

PubMed ID: 8662798

DOI: 10.1074/jbc.271.22.13110

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1832556

Title: Structural organization and the transcription initiation site of the human hepatocyte growth factor gene.

PubMed ID: 1832556

DOI: 10.1021/bi00102a007

PubMed ID: 1826837

Title: Identification of the N-terminal residue of the heavy chain of both native and recombinant human hepatocyte growth factor.

PubMed ID: 1826837

DOI: 10.1016/0006-291x(91)91616-k

PubMed ID: 1482348

Title: Hepatocyte growth factor is linked by O-glycosylated oligosaccharide on the alpha chain.

PubMed ID: 1482348

DOI: 10.1016/0006-291x(92)90219-b

PubMed ID: 1321034

Title: Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.

PubMed ID: 1321034

DOI: 10.1002/j.1460-2075.1992.tb05315.x

PubMed ID: 19576567

Title: Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39.

PubMed ID: 19576567

DOI: 10.1016/j.ajhg.2009.06.003

PubMed ID: 20977675

Title: TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor.

PubMed ID: 20977675

DOI: 10.1111/j.1742-4658.2010.07894.x

PubMed ID: 22242148

Title: SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.

PubMed ID: 22242148

DOI: 10.1371/journal.pone.0027922

PubMed ID: 9493272

Title: The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site.

PubMed ID: 9493272

DOI: 10.1016/s0969-2126(98)00012-4

PubMed ID: 9817840

Title: Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0-A resolution.

PubMed ID: 9817840

DOI: 10.1016/s0969-2126(98)00138-5

PubMed ID: 15167892

Title: Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor.

PubMed ID: 15167892

DOI: 10.1038/sj.emboj.7600243

PubMed ID: 20624990

Title: Structural basis for agonism and antagonism of hepatocyte growth factor.

PubMed ID: 20624990

DOI: 10.1073/pnas.1005183107

Sequence Information:

  • Length: 728
  • Mass: 83134
  • Checksum: 2D997938295ADD2F
  • Sequence:
    • MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 
TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 
NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP 
RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP 
HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKTCAD NTMNDTDVPL 
ETTECIQGQG EGYRGTVNTI WNGIPCQRWD SQYPHEHDMT PENFKCKDLR ENYCRNPDGS 
ESPWCFTTDP NIRVGYCSQI PNCDMSHGQD CYRGNGKNYM GNLSQTRSGL TCSMWDKNME 
DLHRHIFWEP DASKLNENYC RNPDDDAHGP WCYTGNPLIP WDYCPISRCE GDTTPTIVNL 
DHPVISCAKT KQLRVVNGIP TRTNIGWMVS LRYRNKHICG GSLIKESWVL TARQCFPSRD 
LKDYEAWLGI HDVHGRGDEK CKQVLNVSQL VYGPEGSDLV LMKLARPAVL DDFVSTIDLP 
NYGCTIPEKT SCSVYGWGYT GLINYDGLLR VAHLYIMGNE KCSQHHRGKV TLNESEICAG 
AEKIGSGPCE GDYGGPLVCE QHKMRMVLGV IVPGRGCAIP NRPGIFVRVA YYAKWIHKII 
LTYKVPQS