HGF Protein, Human (CHO)

Human hepatocyte growth factor (HGF) is a natural ligand of Met tyrosine kinase receptor, mediating cell proliferation, migration and anti-apoptosis by binding to Met receptor. HGF protein can promote the regeneration of liver and kidney cells, regulate extracellular matrix metabolism (inhibit TGF-β, promote MMP-2), and is used in the study of acute and chronic kidney disease, liver fibrosis and other diseases. HGF Protein, Human (CHO) is a recombinant human HGF protein expressed by CHO cells with tag-free.

1. Characteristics of HGF protein
Human hepatocyte growth factor (HGF) is a heterodimeric protein formed by disulfide bonds between α chain and β chain, belonging to the growth factor family. Its α chain contains a hairpin domain and four kringle domains, and the β chain contains a serine protease-like domain, but lacks protease activity. HGF is a natural ligand for Met tyrosine kinase receptor, and the kringle domain in its structure is essential for receptor binding. In addition, there is a 5-amino-acid deletion type variant of HGF protein, and its biological activity may be changed due to structural differences. HGF activates downstream signaling pathways by binding to Met receptors, mediating cell proliferation, migration, morphogenesis (such as tubulogenesis) and anti-apoptotic effects. HGF can promote the regeneration of various tissue cells such as hepatocytes and kidney cells, regulate extracellular matrix (ECM) metabolism (such as inhibiting collagen deposition and promoting MMP-2 expression), and exert anti-fibrotic effects by inhibiting the production of transforming growth factor TGF-β.
HGF relies on high affinity binding of Met receptors upstream (KD value 20-30 pM), and activates signaling molecules downstream including STAT3, ERK1/2, etc., thereby regulating cell cycle and gene expression. In addition, HGF binds to heparan sulfate proteoglycans (HSPGs) as an extracellular reservoir to regulate their biological activity.

2. Application of HGF protein
HGF can be used in the study of acute kidney injury (AKI), chronic kidney disease (CKD) and diabetic nephropathy. It can inhibit the increase of blood urea nitrogen (BUN) in kidney disease models, reduce tubular damage and glomerular sclerosis, and renal damage does not affect its pharmacokinetics. HGF also promotes liver regeneration (such as acute liver failure and liver fibrosis), and can enhance liver repair and improve liver function when combined with bone marrow mononuclear cells (BMMCs). HGF also alleviates glomerular and liver tissue fibrosis by inhibiting excessive deposition of TGF-β and ECM; it promotes cell migration and differentiation, and exerts anti-fibrotic activity. In clinical studies, recombinant human HGF protein has entered Phase I clinical trials for fulminant hepatitis.

1.The ED₅₀ is <10 ng/mL as measured by 4MBr5 cells, corresponding to a specific activity of >1 × 10⁵ units/mg.
2.Measured by its ability to induce IL-11 secretion by Saos-2 human osteosarcoma cells. The ED₅₀ for this effect is <5.34 ng/mL, corresponding to a specific activity is >1.87×10⁵ U/mg.

• 
  Measured by its ability to induce IL-11 secretion by Saos‑2 human osteosarcoma cells. The ED₅₀ for this effect is 5.34 ng/ml, corresponding to a specific activity is 1.87×10⁵ U/mg.

Human

CHO

Tag Free

P14210-1 (Q32-S728)

3082  [NCBI]

QRKRRNTIHEFKKSAKTTLIKIDPALKIKTKKVNTADQCANRCTRNKGLPFTCKAFVFDKARKQCLWFPFNSMSSGVKKEFGHEFDLYENKDYIRNCIIGKGRSYKGTVSITKSGIKCQPWSSMIPHEHSFLPSSYRGKDLQENYCRNPRGEEGGPWCFTSNPEVRYEVCDIPQCSEVECMTCNGESYRGLMDHTESGKICQRWDHQTPHRHKFLPERYPDKGFDDNYCRNPDGQPRPWCYTLDPHTRWEYCAIKTCADNTMNDTDVPLETTECIQGQGEGYRGTVNTIWNGIPCQRWDSQYPHEHDMTPENFKCKDLRENYCRNPDGSESPWCFTTDPNIRVGYCSQIPNCDMSHGQDCYRGNGKNYMGNLSQTRSGLTCSMWDKNMEDLHRHIFWEPDASKLNENYCRNPDDDAHGPWCYTGNPLIPWDYCPISRCEGDTTPTIVNLDHPVISCAKTKQLRVVNGIPTRTNIGWMVSLRYRNKHICGGSLIKESWVLTARQCFPSRDLKDYEAWLGIHDVHGRGDEKCKQVLNVSQLVYGPEGSDLVLMKLARPAVLDDFVSTIDLPNYGCTIPEKTSCSVYGWGYTGLINYDGLLRVAHLYIMGNEKCSQHHRGKVTLNESEICAGAEKIGSGPCEGDYGGPLVCEQHKMRMVLGVIVPGRGCAIPNRPGIFVRVAYYAKWIHKIILTYKVPQS

Single chain:88-99kDa
Alpha chain:62-65kDa
Beta chain:28-34kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE. Human HGF is initially produced as a single, inactive polypeptide and is subsequently cleaved by serine proteases to generate a 69-kDa α chain and a 34-kDa β chain. The free α and β chains then combine to form an active heterodimer through the formation of disulfide bonds between cysteine residues. Under reducing conditions (SDS-PAGE), the protein exhibits apparent molecular masses of 90, 60, and 34 kDa, which correspond to the heavy α chain and the light β chain, respectively, due to glycosylation.

Lyophilized powder

Lyophilized from a 0.22 μm filtered solution of PBS or PBS, pH 7.4, 8% trehalose.

<0.2 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Adachi E, et al. Pharmacokinetics and pharmacodynamics following intravenous administration of recombinant human hepatocyte growth factor in rats with renal injury. Pharmacology. 2014;94(3-4):190-7.  [Content Brief]

  [2]. Esposito C, et al. Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli. Kidney Int. 2005 Jun;67(6):2143-50.  [Content Brief]

  [3]. Jin SZ, et al. Hepatocyte growth factor promotes liver regeneration induced by transfusion of bone marrow mononuclear cells in a murine acute liver failure model. J Hepatobiliary Pancreat Sci. 2011 May;18(3):397-405.  [Content Brief]

  [4]. Mizuno S, et al. Suppressions of chronic glomerular injuries and TGF-beta 1 production by HGF in attenuation of murine diabetic nephropathy. Am J Physiol Renal Physiol. 2004 Jan;286(1):F134-43.  [Content Brief]

  [5]. Ueno S, et al. Exogenous hepatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs. Cancer Chemother Pharmacol. 1996;38(3):233-7.  [Content Brief]