Hepatocyte Growth Factor: Physiology and What Research Reports
Hepatocyte growth factor (HGF) is a mesenchyme-derived glycoprotein that signals through the MET receptor tyrosine kinase on epithelial, endothelial and other cells. Published work has examined HGF in organ development, wound and corneal repair, fibrosis, retinal and microvascular biology, and tumour growth, where MET pathway activation has been linked to proliferation and invasion. This entry summarises what the cited literature reports about HGF physiology and how it is measured, without offering protocols, products or medical guidance.
What Is Hepatocyte Growth Factor?
Hepatocyte growth factor (HGF) is a secreted, multi-domain glycoprotein growth factor named for its original identification as a serum factor that stimulated the division of liver cells. It is produced as an inactive single-chain precursor (pro-HGF) and converted by extracellular proteases into an active two-chain form held together by a disulfide bond. Its principal high-affinity receptor is MET (also written c-Met), a receptor tyrosine kinase expressed on epithelial cells and on several other cell types.
Although the term appears frequently in peptide discussions, HGF is a full-length protein of several hundred amino acids with complex disulfide architecture and glycosylation — biochemically distinct from the short synthetic peptides that dominate that conversation. This page is for educational purposes only and is not medical advice; consult a licensed physician about any health question or treatment decision.
| Feature | What the literature describes |
|---|---|
| Molecule class | Secreted multi-domain glycoprotein growth factor, activated by proteolytic cleavage |
| Receptor | MET receptor tyrosine kinase, with downstream routes including AKT signalling reported in retinal pigment epithelium cells |
| Typical source cells | Mesenchymal and stromal cells, including fibroblasts |
| Typical target cells | Epithelial cells, endothelial cells, pericytes, keratinocytes, tumour cells |
| Common study models | Cell culture, genetically modified animals reviewed in Biomedical Reports, injury and disease models |
Where HGF Is Produced and What It Does in the Body
HGF is classically described as a stromal signal: mesenchymal cells release it, and neighbouring epithelial cells carrying MET respond. That paracrine arrangement places HGF–MET signalling at tissue interfaces where cells must migrate, survive and rebuild structure after injury.
A 2017 review of genetically modified animals summarised the biological roles assigned to HGF–MET signalling across organ systems on the basis of knockout and transgenic models, and researchers used those models to separate developmental requirements from roles in adult tissue maintenance and regeneration (PMID 29188052). Because the same pathway is redeployed in disease, much of the literature describes HGF in two frames at once: a repair signal in injured tissue and a growth signal that tumours can exploit.
MET as the signalling hub
Most reported HGF effects are attributed to MET activation. In a 2024 study of retinal pigment epithelium cells, HGF promoted cell activity through the MET/AKT signalling pathway (PMID 38766346). In mesothelioma cells, researchers reported that transglutaminase 2 enhanced HGF signalling and helped drive the cancer cell phenotype, illustrating how accessory proteins can amplify the same axis (PMID 35319795).
What the Literature Reports
Epithelial repair and inflammation
In a corneal injury model, HGF suppressed inflammation and promoted epithelium repair, and the study framed HGF delivery as a strategy for restoring the injured ocular surface (PMID 28502469). In skin biology, a 2016 report described HGF reducing CXCL10 expression in keratinocytes, pointing to an immunomodulatory effect on a chemokine associated with inflammatory skin conditions (PMID 27718226).
Fibrosis
Fibrosis is one of the longest-running themes in HGF research. A review in Proceedings of the American Thoracic Society examined HGF and lung fibrosis, discussing how the factor has been positioned as a counter-regulatory signal to fibrotic remodelling (PMID 22802291). In an in vitro model of nifedipine-induced gingival overgrowth, researchers reported that HGF exhibited anti-fibrotic effects (PMID 34980825). Both are laboratory and review-level observations rather than demonstrations of clinical benefit.
Retinal and microvascular biology
The eye has been a productive setting for HGF studies because its epithelia and microvessels can be imaged and modelled. A 2021 study in Microvascular Research reported that HGF prevented pericyte loss in diabetic retinopathy models, pericytes being the perivascular cells whose dropout is an early feature of that disease (PMID 33181170). The retinal pigment epithelium work above adds a second ocular cell type in which MET/AKT signalling was implicated (PMID 38766346).
Cancer biology and pathway blockade
The same proliferative and migratory capacities that support repair make HGF–MET signalling relevant to oncology. A 2020 review examined the function of HGF in gastric cancer proliferation and invasion (PMID 32074717). Drug-development work has moved in the opposite direction from supplementation: a humanised anti-HGF monoclonal antibody, YYB-101, inhibited ovarian cancer progression in a 2019 study (PMID 31355133), and a 2023 paper described resistance to the anti-HGF antibody rilotumumab acquired through intracrine HGF signalling inside tumour cells (PMID 36672409).
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Readers encounter HGF in several different kinds of measurement, and the distinctions matter when interpreting a paper:
- Circulating or tissue HGF concentrations — immunoassay measurements used as biomarkers; a 2021 report in the Journal of UOEH examined hepatocyte growth factor in the setting of primary systemic amyloidosis (PMID 34092767).
- Cell-culture stimulation — recombinant HGF added to cultured cells, then readouts of proliferation, migration or signalling phosphorylation, as in the retinal pigment epithelium and keratinocyte studies (PMID 38766346, PMID 27718226).
- Genetic models — knockout and transgenic animals used to establish where the pathway is required, as summarised in a review of genetically modified animals (PMID 29188052).
- Pathway blockade — antibodies against HGF or MET used to test dependence, as with YYB-101 in ovarian cancer models (PMID 31355133).
Why HGF Matters to People Reading Peptide Literature
HGF appears in peptide-adjacent reading for three reasons. First, it is a canonical repair and anti-fibrotic signal, so it is invoked whenever regeneration is discussed (PMID 22802291). Second, it sits upstream of MET, a receptor that oncology drug development has targeted extensively (PMID 36672409). Third, it is a protein rather than a short peptide, which changes how it can be produced, stabilised and delivered — the cited studies used recombinant protein, gene delivery or antibody approaches in laboratory and animal systems, not consumer products.
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Get the appSafety Signals and Adverse Events: What Studies Report
The verified literature summarised here is largely preclinical and does not report human adverse-event tables. The most consistently discussed biological concern is the pathway's dual nature: HGF has been reported to support gastric cancer proliferation and invasion (PMID 32074717), to be amplified by transglutaminase 2 in the mesothelioma cancer cell phenotype (PMID 35319795), and to sustain tumour signalling through an intracrine route that produced resistance to an anti-HGF antibody (PMID 36672409). Any interpretation of HGF as beneficial has to be read alongside that oncology literature.
Limitations of the Evidence
The repair-oriented findings cited here came from cell culture and disease models — corneal injury, gingival fibroblasts, retinal cells and diabetic retinopathy models (PMID 28502469, PMID 34980825, PMID 33181170). Model results do not establish outcomes in people, and none of the cited work describes an HGF regimen for general use. Readers meeting the term in a study abstract are best served by checking which cells, which species and which delivery method the authors actually used.
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- Biological roles of hepatocyte growth factor-Met signaling from genetically modified animals (Biomedical Reports, 2017)
- Hepatocyte growth factor and lung fibrosis (Proceedings of the American Thoracic Society, 2012)
- Hepatocyte growth factor exhibits anti-fibrotic effects in an in vitro model of nifedipine-induced gingival overgrowth (Journal of Oral Science, 2022)
- Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury (Molecular Therapy, 2017)
- Hepatocyte growth factor reduces CXCL10 expression in keratinocytes (FEBS Letters, 2016)
- Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway (International Journal of Ophthalmology, 2024)
- Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy (Microvascular Research, 2021)
- Function of hepatocyte growth factor in gastric cancer proliferation and invasion (Yeungnam University Journal of Medicine, 2020)
- Rilotumumab Resistance Acquired by Intracrine Hepatocyte Growth Factor Signaling (Cancers, 2023)
- Humanized Anti-hepatocyte Growth Factor Monoclonal Antibody (YYB-101) Inhibits Ovarian Cancer Progression (Frontiers in Oncology, 2019)
- Transglutaminase 2 enhances hepatocyte growth factor signaling to drive the mesothelioma cancer cell phenotype (Molecular Carcinogenesis, 2022)
- Hepatocyte Growth Factor and Primary Systemic Amyloidosis (Journal of UOEH, 2021)
Frequently asked questions
What is hepatocyte growth factor in simple terms?▾
Hepatocyte growth factor is a secreted glycoprotein, produced largely by mesenchymal and stromal cells, that signals through the MET receptor tyrosine kinase on epithelial and other cells. It was named for stimulating liver cell division, but reviews of genetically modified animals describe roles for HGF–MET signalling across multiple organ systems (PMID 29188052). It is a full-length protein, not a short synthetic peptide.
What does the literature report about HGF and tissue repair?▾
In a corneal injury model, researchers reported that HGF suppressed inflammation and promoted epithelium repair (PMID 28502469). A separate study reported that HGF reduced CXCL10 expression in keratinocytes, a chemokine linked to inflammatory skin activity (PMID 27718226). Both findings came from experimental models, so they describe biology observed in the laboratory rather than outcomes established in people.
Why is HGF discussed alongside fibrosis?▾
HGF has long been positioned as a counter-regulatory signal to fibrotic remodelling. A review examined HGF and lung fibrosis and the mechanisms proposed for that relationship (PMID 22802291), and a 2022 study reported anti-fibrotic effects of HGF in an in vitro model of nifedipine-induced gingival overgrowth (PMID 34980825). These are review and cell-culture findings, not clinical demonstrations.
How does HGF relate to cancer research?▾
MET pathway activation supports proliferation and migration, so HGF appears throughout oncology literature. A review examined HGF in gastric cancer proliferation and invasion (PMID 32074717), transglutaminase 2 was reported to enhance HGF signalling in the mesothelioma cancer cell phenotype (PMID 35319795), and drug development has tested anti-HGF antibodies, including YYB-101 in ovarian cancer models (PMID 31355133).
Has blocking HGF been studied as a drug strategy?▾
Yes. A humanised anti-HGF monoclonal antibody, YYB-101, inhibited ovarian cancer progression in a 2019 study (PMID 31355133). A 2023 paper reported resistance to the anti-HGF antibody rilotumumab arising from intracrine HGF signalling within tumour cells (PMID 36672409). Those papers illustrate that much clinical-stage interest has focused on reducing, not increasing, HGF–MET activity.
How is HGF measured in studies?▾
Approaches include immunoassay measurement of HGF concentrations in blood or tissue, as in a report examining hepatocyte growth factor in primary systemic amyloidosis (PMID 34092767); recombinant HGF added to cultured cells with signalling readouts, as in retinal pigment epithelium work implicating MET/AKT (PMID 38766346); and knockout or transgenic animals reviewed for pathway requirements (PMID 29188052).
What do studies report about safety concerns with HGF?▾
The cited literature is mostly preclinical and does not provide human adverse-event data. The recurring biological concern is that the same pathway supporting repair also supports tumour behaviour: HGF was reported to contribute to gastric cancer proliferation and invasion (PMID 32074717) and to sustain tumour signalling that produced antibody resistance (PMID 36672409). This page is educational only; clinical questions belong with a licensed physician.
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References
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.