Follistatin 344 (1mg)

Follistatin 344 Research

Follistatin 344 (FS344) is a variant of the follistatin protein, which is known for its role in inhibiting myostatin, a protein that negatively regulates muscle growth. This makes FS344 a subject of interest in both therapeutic applications and performance enhancement research contexts. FS344 is one of the two main isoforms of follistatin, the other being FS317, both of which arise from alternative splicing of the follistatin precursor mRNA.

Follistatin and Muscle Disorders

FS344 has shown promise in gene therapy for muscle disorders such as Becker muscular dystrophy. Its ability to increase muscle mass by inhibiting the myostatin pathway has been demonstrated in preclinical studies, and clinical trials are exploring its potential as a genetic enhancer to improve muscle function.¹

Follistatin and Muscle Hypertrophy

Follistatin (FS) is a potent inhibitor of myostatin, a negative regulator of muscle growth, and has been shown to induce significant muscle hypertrophy. The hypertrophic effects of FS are mediated through multiple pathways, including the inhibition of myostatin and activin, both members of the TGF-beta superfamily. FS overexpression leads to increased muscle mass by promoting satellite cell proliferation and inhibiting these growth inhibitors.²

FS-induced muscle hypertrophy also has beneficial effects on neuromuscular function, particularly in aged mice. Overexpression of FS improves neuromuscular junction innervation and function, countering age-related degeneration, although it does not prevent motor unit loss.³

Follistatin in Chronic Kidney Disease (CKD)

The therapeutic potential of follistatin in CKD is highlighted by its ability to ameliorate fibrosis and improve kidney function in experimental models⁴. Follistatin administration has been shown to protect against diabetic kidney disease by attenuating early disease markers such as albuminuria and glomerular matrix accumulation⁵. Additionally, inhibition of miR299a-5p, which suppresses the antifibrotic actions of follistatin, offers a novel therapeutic approach for CKD by protecting against renal fibrosis⁶.

Effects on Vascular Function

Studies using spontaneously hypertensive rats (SHR) have demonstrated that follistatin treatment lowers BP and enhances vascular health. This is achieved through the reduction of vascular ROS, improvement in endothelium-dependent relaxation, and inhibition of hypercontractility. Follistatin also reduces the size of adipocytes and increases the expression of brown adipose tissue markers, indicating a shift from white to brown PVAT, which is beneficial for vascular function.⁷

Follistatin as a Metastasis Suppressor

Research indicates that follistatin may act as a metastasis suppressor in breast cancer. In a mouse model of HER2-positive breast cancer, overexpression of follistatin was shown to block the formation of lung metastases, although it did not affect primary tumor growth⁸. This suggests that follistatin could be a target for therapeutic strategies aimed at preventing metastatic progression in breast cancer.

References

1. Al-Zaidy, S., Sahenk, Z., Rodino-Klapac, L., Kaspar, B., & Mendell, J. (2015). Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy. Journal of Neuromuscular Diseases, 2, 185 – 192. https://doi.org/10.3233/JND-150083.
2. Gilson, H., Schakman, O., Kalista, S., Lause, P., Tsuchida, K., & Thissen, J. (2009). Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin.. American journal of physiology. Endocrinology and metabolism, 297 1, E157-64 . https://doi.org/10.1152/ajpendo.00193.2009.
3. Iyer, C., Chugh, D., Bobbili, P., J., A., Crum, A., Yi, A., Kaspar, B., Meyer, K., Burghes, A., & Arnold, W. (2021). Follistatin-induced muscle hypertrophy in aged mice improves neuromuscular junction innervation and function. Neurobiology of Aging, 104, 32-41. https://doi.org/10.1016/j.neurobiolaging.2021.03.005.
4. Mehta, N., Gava, Á., Zhang, D., Gao, B., & Krepinsky, J. (2019). Follistatin Protects against Glomerular Mesangial Cell Apoptosis and Oxidative Stress to Ameliorate Chronic Kidney Disease.. Antioxidants & redox signaling. https://doi.org/10.1089/ars.2018.7684.
5. Zhang, D., Gava, Á., Van Krieken, R., Mehta, N., Li, R., Gao, B., Desjardins, E., Steinberg, G., Hawke, T., & Krepinsky, J. (2019). The caveolin-1 regulated protein follistatin protects against diabetic kidney disease.. Kidney international. https://doi.org/10.1016/J.KINT.2019.05.032.
6. Mehta, N., Li, R., Zhang, D., Soomro, A., He, J., Zhang, I., MacDonald, M., Gao, B., & Krepinsky, J. (2021). miR299a-5p promotes renal fibrosis by suppressing the antifibrotic actions of follistatin. Scientific Reports, 11. https://doi.org/10.1038/s41598-020-80199-z.
7. Kuganathan, A., Lu, V., Gao, B., Macdonald, M., Dickhout, J., & Krepinsky, J. (2024). Abstract P448: Follistatin Improves Vascular Function by Regulating Perivascular Adipose Tissue in Essential Hypertension. Hypertension. https://doi.org/10.1161/hyp.81.suppl_1.p448.
8. Seachrist, D., Sizemore, S., Johnson, E., Abdul-Karim, F., Bonk, K., & Keri, R. (2017). Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer. Breast Cancer Research, 19. https://doi.org/10.1186/s13058-017-0857-y.