Lylybell Zhou

Lylybell Zhou

Small molecules as a novel approach to treat fatty fibrosis


Lylybell Zhou, Alessandra Norris, and Daniel Kopinke PhD


Daniel Kopinke PhD


College of Medicine


<p>Skeletal muscle has a remarkable ability to regenerate upon injury. However, in conditions such as muscular dystrophies and diabetes, muscle tissue is replaced by fibrotic scar and fat tissue, a process called fatty fibrosis. Currently, there are no known treatments for fatty fibrosis. To develop novel therapeutic interventions, it is essential to understand the exact molecular mechanism for why and how fatty fibrosis forms. Previous studies point to the Hedgehog (Hh) pathway as a possible target. Our lab and others have shown that activating Hh promotes muscle regeneration and inhibits fat infiltration, but this mechanism is also not fully understood. In this project, we explore the use of small molecules to modulate the Hedgehog pathway as a novel approach for studying fatty fibrosis. By using the small molecule Smoothened agonist (SAG) to activate Hh, I found that SAG dramatically decreases in intramuscular fat infiltration after injury. By performing qRT-PCR analysis of the injured muscle and examining the expression of key Hh target genes <i>Gli1</i> and <i>Ptch1</i>, I confirmed that SAG successfully and efficiently activates Hh. Therefore, my results demonstrate that SAG successfully activates the Hh pathway and can, thus, be a valuable tool for studying Hh. Future experiments will test the use of the FDA approved drug, vismodegib, as a way to inactivate Hedgehog in a variety of disease models. Together, the results of my project will establish the usefulness of modulating the Hh pathway via small molecules as novel therapeutic approaches for controlling and limiting fatty fibrosis.</p>


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