GFER (Growth Factor, Augmenter of Liver Regeneration), also known as ALR, ERV1, HERV1, HPO, and HSS, is a critical protein involved in mitochondrial function, oxidative phosphorylation, and liver regeneration. This hepatotrophic factor is encoded by the GFER gene located on chromosome 16 and shares functional homology with the yeast scERV1 gene. Its role in maintaining mitochondrial integrity and supporting cellular regeneration makes it a focal point in both basic research and therapeutic development .
Liver Regeneration: Enhances hepatocyte proliferation and survival, contributing to the liver’s exceptional regenerative capacity .
Mitochondrial Maintenance: Supports oxidative phosphorylation and mitochondrial genome stability, akin to its yeast homolog scERV1 .
Stem Cell Regulation: Restricts pluripotent and hematopoietic stem cell proliferation while maintaining mitochondrial integrity .
MAPK/STAT3 Pathway: Inhibition of the 15-kDa isoform reduces p44/42 and STAT3 phosphorylation, blocking cell cycle progression in multiple myeloma (MM) cells .
Cell Cycle Control: Downregulation of CDK1 and cyclin D1 induces S-phase arrest in MM cells .
Differentially Expressed Genes: 289 upregulated, 138 downregulated upon anti-ALR monoclonal antibody treatment .
Enriched Pathways: Pyrimidine metabolism, Fanconi anemia, and oocyte meiosis .
| Tissue | Expression Level | Source |
|---|---|---|
| Liver | High | Hepatocytes |
| Kidney | Moderate | BioGPS data |
| Testis | Moderate | BioGPS data |
| Brain | Low | Allen Brain Atlas |
Hepatocellular Carcinoma: Elevated expression linked to tumor progression .
T-Cell Leukemia: Overexpression observed, suggesting protective roles .
Antibodies: Monoclonal antibodies (e.g., MAB7940) detect GFER in Western blot and IHC, validating its presence in hepatocytes and liver tissue .
RNA-Seq: Used to assess differential gene expression in ALR-targeted therapies .
| Parameter | Detail |
|---|---|
| Formulation | 0.25 mg/mL in Tris-HCl buffer (pH 8.0), 0.2M NaCl, 50% glycerol, 2mM DTT |
| Stability | Store at -20°C; avoid freeze-thaw cycles |
| Purity | >90% (SDS-PAGE) |
GFER (Growth Factor, Augmenter of Liver Regeneration) is a multifunctional protein encoded by the GFER gene, playing critical roles in mitochondrial function, cellular redox regulation, and tissue regeneration. Below are structured FAQs addressing key research considerations:
Data contradiction resolution:
Context-dependent effects: GFER’s yeast homolog (scERV1) is essential for oxidative phosphorylation, but human GFER shows tissue-specific modulation (e.g., liver vs. skeletal muscle) .
Experimental variables: Studies using GFER-knockout models (e.g., CRISPR/Cas9 in HepG2 cells) vs. overexpression systems yield divergent results. Validate with dual-luciferase assays under varying redox conditions .
Advanced model selection:
Partial hepatectomy (PHx) in mice: Monitor liver mass recovery and GFER serum levels (peaking at 24–48h post-PHx) .
Mitochondrial myopathy models: Use GFER R194H mutant knock-in mice to study progressive muscle degeneration and respiratory chain deficiencies .
Proteomic workflow:
Co-IP/MS: Immunoprecipitate GFER from HEK293T lysates using anti-GFER antibodies, followed by mass spectrometry to identify partners like BNIPL and COP9 .
Functional validation: Apply siRNA knockdown of interactors (e.g., BNIPL) and assess GFER-dependent pathways (e.g., TNF-α signaling) via phospho-kinase arrays .
Mechanistic dissection:
Dose-response studies: Treat primary hepatocytes with recombinant GFER (0.1–100 ng/mL) and measure Caspase-3/7 activity vs. BrdU incorporation .
Pathway inhibition: Use JNK inhibitor SP600125 to isolate GFER’s pro-survival effects in ER-stress models .
Translational pipeline:
The Augmenter of Liver Regeneration (ALR), also known as hepatopoietin or hepatic stimulatory substance, is a growth factor that plays a crucial role in liver regeneration. It was initially identified for its ability to promote the growth of hepatocytes in the regenerating or injured liver . ALR is expressed ubiquitously in all organs, but in the liver, it is exclusively found in hepatocytes .
The discovery of ALR marked a significant advancement in understanding liver regeneration. The liver has a unique ability to regenerate itself after injury, which is essential for maintaining its vital functions in metabolism and detoxification . ALR was found to be a key player in this regenerative process, making it a focal point for research aimed at developing therapies for liver diseases and injuries.
ALR functions by stimulating the proliferation of hepatocytes, the primary cells of the liver. It acts through various signaling pathways that are triggered by cytokines and other growth factors . These pathways are crucial for initiating and sustaining the regenerative process, ensuring that the liver can recover from damage and continue to perform its essential functions.
The recombinant form of ALR, known as human recombinant ALR, has been developed to harness its regenerative properties for therapeutic purposes. This form is produced using recombinant DNA technology, which allows for the large-scale production of the protein. Human recombinant ALR has shown promise in preclinical studies for its ability to enhance liver regeneration and improve outcomes in liver injury models .
Research on ALR continues to evolve, with ongoing studies aimed at elucidating its full range of functions and potential therapeutic applications. Scientists are exploring the use of ALR in combination with other growth factors and cytokines to enhance its regenerative effects . Additionally, there is interest in understanding how ALR interacts with other cellular processes and its potential role in treating chronic liver diseases .