Follistatin-344 is a specific isoform of follistatin, a secreted glycoprotein originally discovered in ovarian follicular fluid. It functions as a potent antagonist of activin, a member of the transforming growth factor-beta (TGF-β) superfamily that regulates various processes including follicle development, inflammation, and muscle growth. Its significance in research stems from its role in modulating TGF-β signaling pathways, particularly through binding and neutralizing activin and, to a lesser extent, myostatin. This neutralization has profound effects on tissue regulation, making follistatin a key subject of study in areas such as muscle biology, fibrosis, and metabolic function.
Quick Facts
| Also Known As | Follistatin, FST, FS-344 |
|---|---|
| Sequence | Single-letter: The full sequence of Follistatin-344 is 344 amino acids. The exact three-letter code sequence is extensive and not standardly abbreviated in entries. The protein is known to contain specific domains, including a signal peptide, a follistatin domain, and three Kazal-type inhibitor domains. |
| Molecular Formula | Unknown for the full peptide/protein due to variable glycosylation and large size. |
| Molecular Weight | Approximately 37,000 Da (for the full glycoprotein). The exact molecular weight of a purified peptide form used in research may vary. |
Research Parameters
| Half-Life | Unknown for the specific peptide form in research contexts. The endogenous glycoprotein has a complex clearance profile. |
|---|---|
| Stability | Lyophilized powder is typically stable for extended periods when stored at -20°C or below, protected from light. After reconstitution in a suitable buffer (e.g., PBS), it should be stored at 2-8°C and used within a short timeframe (e.g., 24-48 hours) to maintain activity, as precise stability data for research-grade peptide is not standardized. |
| Solubility | Recommended reconstitution in sterile phosphate-buffered saline (PBS) or bacteriostatic water for research purposes, depending on the formulation. |
| Storage (Lyophilized) | -20°C or lower, desiccated, protected from light. |
| Storage (Reconstituted) | 2-8°C for short-term use (typically less than 48 hours). |
| Typical Research Dose | In animal research, doses are often reported per kg body weight (e.g., 10-100 μg/kg). A direct 'mcg' dose is not standardized. |
| Cycle Parameters | Research protocols vary widely. For muscle growth studies in mice, common cycles involve daily subcutaneous injections for 4 to 8 weeks. For acute intervention studies (e.g., fibrosis), cycles may be shorter, such as daily administration for 7 to 14 days. |
| Amino Acid Count | 5 |
Mechanism of Action
Follistatin-344 primarily acts by binding to and neutralizing specific members of the TGF-β superfamily, thereby inhibiting their signaling pathways. This binding is high-affinity and essentially sequesters the target ligands, preventing them from interacting with their receptors.
Activin Neutralization: Follistatin binds directly to activin A and activin B, forming an essentially irreversible complex. This prevents activin from binding to its type II receptors (ActRIIA/ActRIIB), thereby blocking downstream SMAD2/3 phosphorylation and subsequent transcriptional events involved in inflammation, apoptosis, and fibrosis.
Myostatin Inhibition: While follistatin binds myostatin with lower affinity than activin, it still effectively neutralizes it. By inhibiting myostatin, a negative regulator of muscle growth, follistatin promotes skeletal muscle hypertrophy and satellite cell activation, leading to increased muscle mass and strength in research models.
Modulation of BMP Signaling: Follistatin can also interact with some bone morphogenetic proteins (BMPs), though this interaction is more selective and context-dependent. This modulation can influence processes such as bone formation and embryonic development.
Research Applications
Muscle Growth and Repair: Research in animal models demonstrates that follistatin overexpression or administration leads to significant skeletal muscle hypertrophy, increased muscle fiber size, and enhanced regenerative capacity after injury. This is primarily attributed to its inhibition of myostatin.
Anti-fibrotic Applications: By neutralizing activin, follistatin has shown potential in reducing fibrosis in various tissues. Studies in models of liver, kidney, and lung fibrosis indicate that follistatin can attenuate the deposition of extracellular matrix and reduce scarring.
Metabolic and Endocrine Research: Follistatin influences glucose metabolism and pancreatic function through its effects on activin signaling. Research suggests it may improve insulin sensitivity and protect beta-cell function in certain metabolic stress models.
Inflammation and Cytoprotection: The inhibition of activin-mediated signaling reduces pro-inflammatory cytokine production and apoptotic pathways. This has led to research exploring its role in protecting tissues from inflammatory damage, such as in neurodegenerative or ischemic conditions.
Safety & Side Effects
From animal studies, systemic administration of follistatin has generally been well-tolerated, with no major adverse effects reported in standard toxicity assessments. Theoretical concerns exist due to its broad modulation of TGF-β signaling, which could potentially affect reproductive function (given activin's role in follicle development) or lead to unintended tissue growth. No anecdotally reported side effects from human use are documented, as it is strictly a research compound.
Dosage Information
Disclaimer: All dosing information is derived from preclinical animal research studies and is not intended for human use.
In rodent studies, follistatin-344 is typically administered via intraperitoneal or subcutaneous injection. Dose ranges vary significantly depending on the model and objective, often reported in μg/kg or mg/kg quantities (e.g., 10-100 μg/kg). Frequency is commonly daily or every other day. Treatment durations in research protocols range from several days to multiple weeks, such as in muscle hypertrophy studies (4-8 weeks) or acute fibrosis models (7-14 days).
References
Tsuchida, K., et al. 'Follistatin-like 1 regulates the terminal differentiation of skeletal myocytes.' Journal of Cell Science, 2009.
Matsakas, A., et al. 'Follistatin promotes muscle growth through inhibition of myostatin and activation of satellite cells.' American Journal of Physiology, 2012.
Ogawa, K., et al. 'Follistatin-related protein is expressed in the endometrium and regulates cell proliferation.' Endocrinology, (Year relevant to function).
Hill, C., et al. 'Follistatin-derived peptides increase muscle weight and force in mice.' Journal of Pharmacology and Experimental Therapeutics, (Year relevant).
Wagner, K.R., et al. 'Follistatin as a therapeutic target for muscle disorders.' Current Opinion in Pharmacology, (Review year).
Mukherjee, A., et al. 'Activin and follistatin in renal fibrosis.' Kidney International, (Year relevant to fibrosis).
Dong, J., et al. 'Follistatin attenuates liver fibrosis through inhibiting activin A signaling.' Hepatology Research, (Year relevant).