FST Human, His
Description
Functional Roles and Mechanism of Action
FST Human, His acts as a high-affinity antagonist of activin and myostatin by binding directly to these ligands, preventing receptor interactions .
Key Mechanisms:
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TGF-β Superfamily Regulation: Neutralizes activin A/B and BMPs, impacting cellular differentiation and proliferation pathways .
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FSH Inhibition: Suppresses pituitary follicle-stimulating hormone (FSH) biosynthesis, influencing reproductive physiology .
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Muscle Growth Modulation: By inhibiting myostatin (GDF-8), FST promotes muscle hypertrophy, a property explored in therapies for muscular dystrophy and sarcopenia .
Production and Purification Protocols
Expression Systems:
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*E. coli*: Yields non-glycosylated FST-His with a 10-amino-acid N-terminal His tag. Purified via immobilized metal affinity chromatography (IMAC) and formulated in TRIS-NaCl buffer (pH 7.5) .
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Sf9 Baculovirus: Produces glycosylated FST344-His with a C-terminal His tag, purified using proprietary chromatographic methods .
Stability:
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Lyophilized forms remain stable at -20°C for long-term storage. Reconstituted proteins retain activity for up to two weeks at 4°C .
Research Applications and Clinical Relevance
Therapeutic Studies:
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Muscle-Wasting Disorders: Preclinical trials demonstrated that AAV-mediated FST delivery increased muscle mass in murine models of spinal muscular atrophy (SMA) and Duchenne muscular dystrophy .
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Metabolic Diseases: Elevated FST levels correlate with insulin resistance in type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), highlighting its role in metabolic regulation .
Ongoing Clinical Trials:
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ACE-083: A follistatin-based fusion protein showed increased muscle volume in Charcot-Marie-Tooth disease (CMT) models without systemic side effects .
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Post-Traumatic Osteoarthritis: FST therapy reduced inflammation and synovial fluid degradation in murine joint injury models .
Genetic and Population Studies
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Linkage to PCOS: Genome-wide association studies (GWAS) identified FST as a candidate gene linked to polycystic ovary syndrome (PCOS) susceptibility .
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Population Differentiation: Global F<sub>ST</sub> analyses revealed moderate genetic differentiation (mean F<sub>ST</sub> = 0.08) across human populations, with rare variants showing higher differentiation .
Challenges and Future Directions
Product Specs
Product Science Overview
Follistatin is known for its ability to bind and neutralize members of the transforming growth factor-beta (TGF-β) superfamily, particularly activin . By binding to activin, follistatin functions as an activin antagonist, thereby inhibiting the biosynthesis and secretion of pituitary FSH . This interaction is crucial for regulating various physiological processes, including reproductive functions, cell growth, and differentiation .
Follistatin is expressed in numerous tissues beyond the gonads, including the brain, adrenal glands, bone marrow, and placenta . It plays a significant role in early embryogenesis and is involved in local regulatory functions in these tissues . The activin-follistatin system is particularly important in the anterior pituitary, the classical target tissue for inhibin .
Recombinant human follistatin, tagged with a histidine (His) tag, is produced using expression systems such as HEK293 cells . The His tag facilitates purification and detection of the protein. The recombinant protein is typically lyophilized and can be reconstituted for use in various research applications . It is measured for its ability to neutralize activin-mediated inhibition on cell proliferation, with an effective dose (ED50) typically ranging from 5-40 ng/mL .
Recombinant human follistatin is widely used in research to study its role in various biological processes and diseases. It has been linked to conditions such as polycystic ovary syndrome (PCOS) and hyperandrogenemia . Additionally, follistatin’s regulatory roles in extragonadal tissues make it a valuable tool for investigating its functions in different physiological contexts .
Lyophilized recombinant follistatin is stable for up to 12 months when stored at -20 to -80°C . Once reconstituted, the protein solution can be stored at 4-8°C for 2-7 days, and aliquots can be kept at -20°C for up to 3 months . It is typically formulated in sterile PBS with added protectants such as trehalose, mannitol, and Tween80 .
