HGF 蛋白, 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. HGF 蛋白的特点
人肝细胞生长因子 (HGF) 是由 α 链和 β 链通过二硫键连接形成的异二聚体蛋白，属于生长因子家族。其 α 链包含一个发夹结构域和四个 kringle 结构域，β 链含有一个丝氨酸蛋白酶样结构域，但缺乏蛋白酶活性。HGF 是 Met 酪氨酸激酶受体的天然配体，其结构中的 kringle 结构域对受体结合至关重要。此外，HGF 蛋白存在 5 氨基酸缺失的变体 (5-amino-acid deletion type)，其生物活性可能因结构差异而改变。 HGF 通过结合 Met 受体激活下游信号通路，介导细胞增殖、迁移、形态发生 (如肾小管生成) 和抗凋亡效应。HGF 可促进肝细胞、肾细胞等多种组织细胞的再生，调节细胞外基质 (ECM) 代谢 (如抑制胶原沉积、促进 MMP-2 表达)，并通过抑制转化生长因子 TGF-β 的产生发挥抗纤维化作用。
HGF 在上游依赖 Met 受体的高亲和力结合 (KD 值 20-30 pM)，下游激活的信号分子包括STAT3、ERK1/2等，进而调控细胞周期和基因表达。此外，HGF 与硫酸乙酰肝素蛋白聚糖 (HSPG) 结合，作为细胞外储库调节其生物活性。

2. HGF 蛋白的应用
HGF 可用于急性肾损伤 (AKI)、慢性肾病 (CKD) 和糖尿病肾病的研究，可抑制肾脏疾病模型中，血尿素氮 (BUN) 升高，减轻肾小管损伤和肾小球硬化，且肾损伤不影响其药代动力学。HGF 还促进肝再生 (如急性肝衰竭、肝纤维化)，联合骨髓单核细胞 (BMMCs) 可增强肝脏修复，改善肝功能。HGF 还通过抑制 TGF-β 和 ECM 过度沉积，缓解肾小球、肝组织纤维化；促进细胞迁移和分化，发挥抗纤维化活性。临床研究中，重组人 HGF 蛋白已进入暴发性肝炎的 I 期临床试验。

HGF 蛋白 (人源；50 ng/mL；24 h，48 h) 可降低人肾小球中 (a2)IV 胶原、TGF-β 和 TIMP-1 的 mRNA 及蛋白水平，增加 MMP-2 的 mRNA 水平，并上调 c-met 受体的表达^[2]。

HGF 蛋白 (人源；1 mg/kg/day；静脉注射；每日 1 次；7 天) 在 CCl₄ 诱导的急性肝衰竭小鼠模型中，与骨髓单核细胞 (BMMCs) 联合使用时，可显著促进肝再生，表现为 PKH26 标记的 BMMCs 定植增加、增殖细胞核抗原 (PCNA) 和白蛋白表达上调，并改善肝功能^[1]。
HGF 蛋白 (人源；300 μg/kg；皮下注射；每天 2 次；4 周) 在 Streptozotocin (HY-13753) 诱导的糖尿病肾病小鼠模型中，可抑制肾小球肥大和硬化，减少 IV 型胶原和 TGF-β 沉积，降低尿白蛋白排泄，并减轻肾小管间质纤维化^[4]。
HGF 蛋白 (人源；250 ng/kg；门静脉注射；4 次，分别于术后 0.5、12、24、48 h) 在门静脉结扎 (PBL) 的犬模型中，可促进非结扎肝叶的 DNA 合成和肝细胞肥大，增加肝脏重量，且不影响肝功能指标^[5]。

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]

Full Length of Isoform-1 Mature Protein

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.

无菌粉末

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]