Recombinant Human Proheparin-binding EGF-like growth factor [Cleaved into: Heparin-binding EGF-like growth factor protein (HBEGF) (Active)
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Description
Biological Activity and Mechanism of Action
HBEGF signals through EGFR (ErbB1), ErbB2, and ErbB4 receptors, with 10–100x higher affinity for EGFR than EGF itself . Key functional attributes include:
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Mitogenic Activity: Stimulates proliferation of fibroblasts, smooth muscle cells, and keratinocytes (ED₅₀ < 1 ng/ml in BALB/c 3T3 assays) .
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Cardiovascular Roles: Maintains adult heart homeostasis via ErbB2 and promotes cardiac valve development .
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Embryonic Development: Mediates blastocyst implantation through ErbB4 binding .
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Wound Healing: Accelerates epithelialization by enhancing keratinocyte migration .
Research Applications and Findings
HBEGF’s diverse roles have been elucidated through preclinical and clinical studies:
3.1. Cancer Biology
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Tumor Progression: HBEGF overexpression drives epithelial-mesenchymal transition (EMT) in keratinocytes, increasing invasiveness and upregulating MMP1, COX-2, and vimentin .
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Therapeutic Targeting: Peptide inhibitors blocking HBEGF-EGFR interaction reduce ovarian cancer cell viability .
3.2. Autoimmune and Inflammatory Diseases
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Multiple Sclerosis: Astrocyte-derived HBEGF limits CNS inflammation in EAE (experimental autoimmune encephalomyelitis) models by modulating oligodendrocyte and immune cell dynamics .
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COPD and Fibrosis: HBEGF contributes to airway fibrosis by inducing pulmonary epithelial-mesenchymal transition .
3.3. Metabolic and Developmental Roles
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Glucose Regulation: Exercise-induced HBEGF enhances peripheral glucose uptake, potentially mitigating obesity and type 2 diabetes .
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Necrotizing Enterocolitis: HBEGF protects intestinal stem cells, preserving gut barrier function in premature infants .
Comparative Functional Insights
Clinical and Industrial Relevance
Product Specs
Buffer
Lyophilized from a 0.2 µm filtered 20 mM phosphate buffer (PB), pH 7.4, containing 130 mM sodium chloride (NaCl).
Form
Lyophilized powder
Lead Time
5-10 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
It is recommended to briefly centrifuge the vial prior to opening to ensure the contents are at the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. For long-term storage, we recommend adding 5-50% glycerol (final concentration) and aliquoting at -20°C/-80°C. The default final concentration of glycerol is 50%. Customers may use this as a reference.
Shelf Life
The shelf life is influenced by various factors, including storage conditions, buffer ingredients, storage temperature, and the protein's inherent stability.
Generally, the shelf life of the liquid form is 6 months at -20°C/-80°C. The shelf life of the lyophilized form is 12 months at -20°C/-80°C.
Generally, the shelf life of the liquid form is 6 months at -20°C/-80°C. The shelf life of the lyophilized form is 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquoting is necessary for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag-Free
Synonyms
diphtheria toxin receptor (heparin-binding EGF-like growth factor); diphtheria toxin receptor (heparin-binding epidermal growth factor-like growth factor); Diphtheria toxin receptor; DT R; DT-R; DTR; DTS; DTSF; HB-EGF; HBEGF; HBEGF_HUMAN; HEGFL; Heparin binding EGF like growth factor; Heparin binding epidermal growth factor; Heparin binding epidermal growth factor like growth factor; Heparin-binding EGF-like growth factor; Proheparin binding EGF like growth factor
Datasheet & Coa
Please contact us to get it.
Expression Region
63-148aa
Mol. Weight
9.7 kDa
Protein Length
Full Length of Mature Protein
Purity
>97% as determined by SDS-PAGE.
Research Area
Cancer
Source
E.coli
Species
Homo sapiens (Human)
Target Names
Uniprot No.
Target Background
Function
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a growth factor that exerts its effects through the epidermal growth factor receptor (EGFR), ERBB2, and ERBB4. It is essential for normal cardiac valve formation and heart function. HB-EGF promotes smooth muscle cell proliferation and may be involved in macrophage-mediated cellular proliferation. It exhibits mitogenic activity towards fibroblasts but not endothelial cells. HB-EGF binds to the EGF receptor/EGFR with higher affinity than EGF itself and is a significantly more potent mitogen for smooth muscle cells than EGF. Additionally, HB-EGF acts as a receptor for diphtheria toxin.
Gene References Into Functions
- Levels of the angiogenesis mediators endoglin, HB-EGF, BMP-9, and FGF-2 were examined in patients with severe sepsis and septic shock. Endoglin and HB-EGF may play a role in the host response to sepsis. Further research is warranted to investigate their potential as biomarkers or therapeutic targets in sepsis. PMID: 28746898
- HB-EGF plays a pro-inflammatory role in the active skin and lung lesions of systemic sclerosis. PMID: 29044628
- Serum HB-EGF expression may be a potential therapeutic indicator for novel HB-EGF-targeted therapy in recurrent ovarian cancer. PMID: 29970572
- Both HBEGF upregulation and apoptosis were rescued by exogenous MMP2. PMID: 28731464
- Research findings suggest that excessive heparin-binding epidermal growth factor-like growth factor (HB-EGF) leads to a significant increase in vascular endothelial growth factor (VEGF) and ventricular dilatation. These data suggest a potential pathophysiological mechanism where elevated HB-EGF can induce VEGF and hydrocephalus. PMID: 27243144
- These results suggest that HBEGF is a significant EGFR ligand in cervical cancer and that cervical cancer cells are the primary source of HBEGF. Therefore, an autocrine EGFR stimulation model in cervical carcinomas is proposed. PMID: 28498437
- Macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased MMP9 in OVCA433, resulting in a positive feedback loop that drives HB-EGF release and enhances proliferation in co-culture. PMID: 27888810
- Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 x 10(-8)) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1. PMID: 28183528
- HB-EGF is implicated in DNA double-strand breaks repair, as silencing of HB-EGF increased gammaH2AX foci half-life, as well as USP9X expression. These findings suggest a link to the observed effect on Mcl-1. PMID: 28970067
- Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor. PMID: 28174207
- This study suggests that HBEGF promotes the formation of gliomas, is necessary for tumor maintenance, and therefore may be a novel therapeutic target. PMID: 28368403
- Results show that HBEGF is highly expressed in primary ovarian tumors and increases as the disease progresses. PMID: 28668900
- The serous carcinomatous component characterized by HB-EGF expression predisposes to recurrence/metastasis in stage I metastasis and recurrence in stage I uterine malignant mixed mullerian tumor. PMID: 26980026
- Annexin A2 and HB-EGF are overexpressed and secreted into serum in Her-2 negative breast cancer patients. PMID: 27496793
- This study demonstrates that HBEGF is post-transcriptionally regulated by low O2 (placental environment) through a mechanism involving interactions of miRNAs with its 3'UTR. PMID: 27701455
- MMP14 plays a critical mechanistic role in NSCLC progression, supporting cancer invasiveness, promoting collagen degradation, and releasing HB-EGF, which accelerates lung tumor progression. PMID: 28013056
- These results indicate that this new anti-HB-EGF mAb 2-108 would be useful in diagnosing HB-EGF-related cancers and would be a valuable tool in both basic and clinical research on HB-EGF. PMID: 26974561
- This antibody reacts with human HB-EGF but not mouse HB-EGF. No cross-reactivity to other EGFR ligands was observed by antigen ELISA. PMID: 27097072
- HB-EGF is a molecular target for the resistance of ovarian cancer to paclitaxel. CRM197, as a HB-EGF-targeted agent, might be a chemosensitizing agent for paclitaxel-resistant ovarian carcinoma. PMID: 26572150
- Data suggest that placental expression of HBEGF, EGF (epidermal GF), and TGFA (transforming GF alpha) is down-regulated in pre-eclampsia compared to normal term birth. Each growth factor blocks cell death/apoptosis of the cytotrophoblast cell line. PMID: 25589361
- Serum sHB-EGF is closely correlated with advanced stage gastric cancer and may be a promising serological biomarker for GC. PMID: 25717241
- Studies indicate that heparin-binding EGF-like growth factor (HB-EGF) is a therapeutic target in certain types of cancers. PMID: 25517307
- The relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and notably increased following treatment. PMID: 25138066
- Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating the outcome of overactive bladder syndrome treatment. PMID: 25510766
- HB-EGF is a biomarker for LPA1 receptor activation in human breast and prostate cancers. PMID: 24828490
- MiR-212 exerts a suppressive effect on SKOV3 ovarian cancer cells by targeting HBEGF. PMID: 25201063
- High levels of HB-EGF contribute to carotid plaque stabilization and reduce the incidence of acute coronary events. PMID: 25359857
- Autocrine HBEGF expression promotes breast cancer intravasation, metastasis, and macrophage-independent invasion in vivo. PMID: 24013225
- Studies suggest that disintegrin and metalloproteinase domain-containing protein 12 (ADAM 12S) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) are involved in cellular plasticity, resulting in the production of brown adipose tissue-like cells. PMID: 24116709
- Knockdown of HSP27 by shRNA decreased HB-EGF plus CXCL5-mediated tumor spheroid formation in a three-dimensional culture system, suggesting that AKT/HSP27 was required for HB-EGF/CXCL5-mediated cancer progression. PMID: 24346967
- Heparin-binding epidermal growth factor and CD9 are likely implicated in processes highly relevant for MS lesion formation. PMID: 24038577
- HB-EGF acts as a potent paracrine and/or autocrine chemotactic factor, as well as a mitogen that mediates HER1 and/or HER4 in the invasion and metastasis of thyroid carcinoma cells. PMID: 23917679
- Results suggest that HB-EGF plays a pivotal role in the acquisition of tumor aggressiveness in TNBC by orchestrating a molecular hierarchy regulating tumor angiogenesis. PMID: 23443317
- HB-EGF overexpression and Kras(G12D) together, but neither alone, increase cancer cell proliferation. PMID: 23376846
- A correlation has been found between HB-EGF expression/immunostaining and the different types of analyzed soft tissue sarcomas. PMID: 23597914
- The study suggests that one of the causes of unexplained miscarriages may result from impaired expression of heparanase and heparin-binding EGF-like growth factor. PMID: 23907942
- A reciprocal cross-talk between intrahepatic cholangiocarcinoma cells and myofibroblasts through the HB-EGF/EGFR axis contributes to CCA progression. PMID: 23787814
- A mechanism involving a probiotic-derived soluble protein in modulating intestinal epithelial cell homeostasis through ADAM17-mediated HB-EGF release, leading to transactivation of EGFR, has been proposed. PMID: 24043629
- Spatiotemporal regulation of proHB-EGF shedding in individual cells was visualized using a simple method that measures changes in fluorescence ratios. PMID: 23598347
- Results indicate that Abl kinases negatively regulate HNSCC invasive processes through suppression of an HB-EGF autocrine loop responsible for activating an EGFR-Src-cortactin cascade. PMID: 23146907
- Our results show that HB-EGF acts as a cell proliferation and cell survival factor in cancer cells. PMID: 23349913
- Hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling-dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. PMID: 23589494
- HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy. PMID: 22646534
- Expression of HB-EGF in human KCs triggers a migratory and invasive phenotype with many features of epithelial-mesenchymal transition (EMT), which may be beneficial in the context of cutaneous wound healing. PMID: 22592159
- Results suggest that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a target for oral cancer and that CRM197 is effective in oral cancer therapy. PMID: 22718294
- Variant 1936T prevents hsa-miR-1207-5p from down-regulating HBEGF in podocytes. PMID: 22319602
- This study is the first report demonstrating a role for the ADAM-HBEGF-EGF receptor axis in Ox-PAPC induction of IL-8 in HAECs. PMID: 22402363
- These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. PMID: 22136955
- Heparin-binding epidermal growth factor-like growth factor is a potent autocrine regulator of invasion activity in oral squamous cell carcinoma. PMID: 22209887
- Lung cancer-derived galectin-1 enhances the tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor. PMID: 22291012
Database Links
Subcellular Location
[Heparin-binding EGF-like growth factor]: Secreted, extracellular space. Note=Mature HB-EGF is released into the extracellular space and probably binds to a receptor.; [Proheparin-binding EGF-like growth factor]: Cell membrane; Single-pass type I membrane protein.
Q&A
What expression systems are optimal for producing bioactive recombinant HB-EGF?
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Heparin affinity: Glycosylation impacts binding to heparan sulfate proteoglycans
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Proteolytic processing: Furin-mediated cleavage from proHB-EGF requires mammalian secretory pathways
Validation should include:
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N-terminal sequencing to confirm cleavage site integrity
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EGFR phosphorylation assays using A431 epidermoid carcinoma cells
How do researchers validate HB-EGF activity across different cell types?
Standardized protocols from Source 4 and 5 recommend:
Contradictory results often arise from:
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Cell density effects: Subconfluent vs. confluent keratinocytes show 1.8x vs. 2.1x response variance
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Heparan sulfate competition: 10 U/mL heparin pretreatment reduces activity by 38%
How to resolve discrepancies in HB-EGF's dual role in tissue repair vs. pathology?
Source 4 and 5 reveal context-dependent HB-EGF effects requiring advanced experimental design:
Cartilage Degeneration vs. Neuroprotection
Resolution Strategies
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Conditional knockouts: Tissue-specific HB-EGF deletion models
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Microenvironment modulation: Compare 3D matrices (collagen I vs. aggrecan)
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Temporal dosing: Pulse (6h) vs. sustained (72h) exposure in injury models
What experimental controls are critical for in vivo HB-EGF studies?
Source 2 and 5 emphasize:
Critical data normalization required for:
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Blastocyst implantation studies: Synchronize pseudopregnancy stages within ±2h windows
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Ischemia models: Maintain cerebral blood flow at 18-22 mL/100g/min via laser Doppler
Why do HB-EGF dose responses vary between 2D vs. 3D culture systems?
Source 1 and 4 demonstrate matrix-dependent signaling:
| Culture System | Optimal Dose | Maximum Effect | Matrix Component |
|---|---|---|---|
| 2D Keratinocytes | 1 ng/mL | 1.8x proliferation | Type I collagen |
| 3D Chondrocytes | 10 ng/mL | 3.1x MMP-13 release | Agarose (2% w/v) |
Mechanistic basis:
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Receptor clustering: 3D environments enhance ErbB4 homodimerization
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Heparan sulfate sequestration: Matrix-bound HSGAGs limit bioavailability
Experimental Adjustment
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Pre-equilibrate 3D scaffolds with 0.1-1 μg/mL heparin for 24h before HB-EGF treatment
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Use FRET-based EGFR dimerization sensors in live-cell imaging
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