Abstract

Idiopathic pulmonary fibrosis (IPF) is an incurable interstitial lung disease defined by the progressive, irreversible scarring of the tissues between the lung’s alveoli. To date, only two drugs have received approval for treatment. However, these medications are not considered cures since they do not stop the progression of the disease. A deeper understanding of the mechanisms underlying IPF could aid in discovering a cure. We recently found that myocardin (MyoCD) regulates SMAD2/3 transcription factors in the TGF-β signaling pathway and governs the genes involved in pleural fibrosis. However, it is unclear whether MyoCD plays a critical role in IPF by regulating various genes, leading to the differentiation of myofibroblasts. In this study, six novel MyoCD effector genes were examined to determine their potential roles in myofibroblast differentiation and cytoskeletal reorganization of IPF cells stimulated with TGF-β. At the mRNA and protein levels, MyoD Family Inhibitor (MDFI) knockdown (KD) decreased the expression of MyoCD, α-SMA, PAI-1, CNN-1, and FN-1, while COL-1 remained unaffected. This was the main MyoCD effector protein that showed significance in the data. Results from immunocytochemistry confirmed that MDFI influences cytoskeletal changes by reducing the formation of stress fibers. Furthermore, secretion was also affected by MDFI KD. This data suggests that MDFI impacts myofibroblast differentiation and cytoskeletal remodeling in IPF fibroblast cells through the TGF-β/MyoCD signaling pathway; therefore, it may contribute to the progression of IPF.

Date of publication

Spring 5-19-2025

Document Type

Thesis

Language

english

Persistent identifier

http://hdl.handle.net/10950/4855

Committee members

Dr. Osamu Sato, Dr. Pierre Neuenschwander, Dr. Mitsuo Ikebe, Dr. Hua Tang

Degree

Master of Science in Biotechnology

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