First Advisor

Oleh Taratula

Date of Award

Winter 3-22-2025

Document Type

Thesis

Degree Name

Bachelor of Science (B.S.) in Biology and University Honors

Department

Biology

Language

English

Subjects

follistatin, activin A, mRNA therapy, lipid nanoparticles, muscle regeneration

DOI

10.15760/honors.1624

Abstract

Skeletal muscle regeneration and maintenance remain critical challenges in treating various muscular disorders and injuries. While follistatin (FST) has shown promise as a therapeutic agent, its delivery and controlled expression present significant hurdles. This study investigates a mRNA-lipid nanoparticle (LNP) delivery system for FST to enhance muscle healing during regeneration and prevent atrophy. Using a cardiotoxin (CTX)-induced muscle injury model in C2C12 myotubes, we demonstrated that Fst mRNA-LNP treatment significantly protected against cell death and promoted muscle hypertrophy. The treatment maintained cell viability at approximately 6,000 fluorescence units compared to near-zero levels in CTX-only treated cells (P< 0.01) and increased myotube diameter by 30-35% compared to controls (P< 0.0001). Mechanistically, FST acts as a potent antagonist of multiple TGF-β superfamily members, including myostatin and activin A and B, leading to decreased SMAD2/3 phosphorylation and increased Akt phosphorylation. The mRNA-LNP delivery system provided enhanced control over FST expression and improved cellular uptake compared to traditional approaches. These findings provide crucial insights into FST's therapeutic potential and establish a foundation for developing targeted treatments for muscle wasting conditions and injuries.

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Persistent Identifier

https://archives.pdx.edu/ds/psu/43658

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