Hepatocyte Growth Factor (HGF)

Class Peptide growth factor hormoneReceptor MET

Function

Hepatocyte growth factor is a multifunctional peptide signaling hormone involved in tissue regeneration, epithelial repair, cellular migration, angiogenesis, organ development, and regulation of survival signaling pathways. HGF functions as a potent regenerative mediator that supports recovery and structural adaptation following tissue injury.

The hormone stimulates cellular motility, proliferation, morphogenesis, and anti-apoptotic signaling in epithelial and endothelial tissues. HGF also contributes to liver regeneration, wound healing, vascular adaptation, and communication between stromal and epithelial cell populations. Through these actions, it coordinates tissue remodeling and regenerative growth responses in multiple organ systems.

Production

HGF is produced mainly by mesenchymal cells including fibroblasts, stromal cells, smooth muscle cells, endothelial cells, and connective tissue structures. It is synthesized as an inactive precursor that requires proteolytic cleavage to generate biologically active HGF.

Production increases during tissue injury, inflammatory activation, organ regeneration, and wound-healing responses. Local synthesis allows paracrine communication between connective tissue environments and epithelial target cells requiring repair or growth support.

Regulation

HGF production is regulated by inflammatory cytokines, oxidative stress, tissue injury, extracellular matrix remodeling, hypoxia, and regenerative signaling pathways. Mechanical tissue stress and wound-associated signaling can substantially increase expression.

HGF acts through the MET receptor tyrosine kinase located on epithelial cells, endothelial cells, hepatocytes, and additional tissues. Activation stimulates MAP kinase pathways, PI3K-AKT signaling, STAT pathways, and cytoskeletal remodeling systems involved in migration and survival responses. Receptor degradation and phosphatase-mediated pathways help regulate signaling duration. Through these integrated regenerative signaling systems, HGF coordinates tissue repair, epithelial regeneration, angiogenesis, and structural adaptation after injury.

Identity & Secretion

Primary Source GlandNo single endocrine gland; produced by mesenchymal/stromal cells, fibroblasts, macrophages.
Secretion PatternContext-dependent; rises with injury/repair cues, mechanical stress, and paracrine stromal signaling.
PrecursorPro-HGF → HGF (α/β chains) activated by extracellular proteases (e.g., HGFAC)

Nutrient Requirements

Nutrient Precursors
  • Dietary amino acids for peptide synthesis; matrix proteins and redox milieu modulate activation and signaling.
Required Vitamins
  • Vitamin C (matrix/collagen environment), Folate, B6 (amino acid/one-carbon metabolism)
Required Minerals
  • Magnesium, Zinc, Copper (enzyme/signaling cofactors)

Key Foods

  • Leafy greens, legumes, whole grains, citrus/berries, nuts and seeds, beets (support antioxidant status and matrix balance).

Targets & Signaling

Target Tissues
  • Liver, epithelium, endothelium, kidney, lung, muscle, and other repairing tissues
Feedback Loops
  • Balanced by extracellular activation/inhibition, receptor endocytosis, and matrix sequestration (non-medical context).
Second Messengers
  • Phosphorylation cascades downstream of RTK; intracellular Ca²⁺/DAG via PLCγ; small GTPase signaling.
Pathways Involved
  • RTK → RAS-RAF-MEK-ERK (MAPK); RTK → PI3K-Akt; STAT3; PLCγ-PKC; cross-talk with integrin/FAK and Rho GTPases.

Key Functions

  • Epithelial/microvascular repair, branching morphogenesis, cell survival, controlled motility, and tissue regeneration.

Plant-Based Focus

  • Whole-food, antioxidant-rich plant patterns support redox and matrix environments compatible with normal repair signaling (context only).

Clinical Context

Assay Notes
Sample handling and platelet content can alter measured HGF; assays may detect total vs. active forms.

Linked Knowledge

Phytochemicals
  • Quercetin, resveratrol, EGCG, curcumin (studied for RTK/ MET-axis modulation in research contexts).
Amino Acids
  • Glycine, proline (matrix protein contexts); arginine (NO milieu)
Foods
  • Leafy greens, legumes, oats/quinoa, berries, citrus, walnuts, flaxseed, pumpkin seeds, beetroot
Vitamins
  • Vitamin C, Folate, B6
Minerals
  • Magnesium, Zinc, Copper
Cancers (context)
  • HGF–MET axis widely discussed in tumor microenvironment and invasion literature (context only).
Ailments
  • Tissue repair and regeneration physiology, epithelial barrier recovery (context only).

Dietary Modulators

  • Plant patterns high in fiber/antioxidants support balanced redox and matrix signaling (context only).

Inhibitors / Activators

Inhibitors
  • Highly processed, pro-oxidative dietary patterns may alter redox/matrix environments (context only).
Activators
  • Physiologic mechanical stress, injury/repair cues, and extracellular protease activation of pro-HGF.

Summary

HGF coordinates epithelial repair, controlled motility, and survival via MET-mediated RTK signaling.

SUMMARY OF EFFECTS ON THE BODY

Supports organized tissue regeneration and barrier restoration within physiological limits.

Research

General RTK/MET biology and organ repair reviews (physiology).
Created: Nov 11, 2025 Updated: May 27, 2026