Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by fibroblast activation, excessive extracellular matrix (ECM) deposition, and irreversible respiratory decline. In this study, we investigated the role of myocardin and its downstream effectors, RGS5, DLGAP5, and TAGLN, in thrombin-induced myofibroblast differentiation and ECM remodeling using primary human IPF fibroblasts. Myocardin knockdown significantly attenuated thrombin-induced expression of profibrotic genes, including FN1, COL1A1, PAI-1, ACTA2, and CNN1, as well as the novel effectors RGS5, DLGAP5, and TAGLN, confirming myocardin as a central regulator of fibrotic signaling. Silencing RGS5 produced minimal effects on gene and protein expression despite minor downward trends. In contrast, DLGAP5 knockdown selectively reduced fibronectin, calponin1, and α-SMA expression, indicating a role in ECM regulation and myofibroblast differentiation. TAGLN knockdown similarly decreased calponin1 and α-SMA levels and disrupted actin stress fiber organization, suggesting an important function in cytoskeletal remodeling. Protein analyses confirmed reduced α-SMA expression following DLGAP5 and TAGLN silencing, while wound healing assays demonstrated impaired migratory capacity in TAGLN-deficient cells. Collectively, these findings identify myocardin as a key mediator of thrombin-driven profibrotic responses in IPF fibroblasts and establish TAGLN and DLGAP5 as important downstream effectors involved in cytoskeletal dynamics and ECM remodeling. Targeting the myocardin signaling axis may therefore represent a promising therapeutic strategy for limiting IPF progression.
Date of publication
Spring 5-14-2026
Document Type
Thesis
Language
english
Persistent identifier
http://hdl.handle.net/10950/5069
Committee members
Sato Osamu (Thesis Advisor), Amy Tvinnereim (Commitee Chairperson), Mitsuo Ikebe, Pierre Neuenschwander, Torry Tucker, Hua Tang,
Degree
Master of Science in Biotechnology (Cellular and Molecular Biology)
Recommended Citation
Okeke, Christiana, "THROMBIN-INDUCED MYOFIBROBLAST DIFFERENTIATION IS REGULATED BY MYOCARDIN AND NOVEL EFFECTOR GENES IN IPF FIBROBLASTS" (2026). Biotechnology Theses. Paper 40.
http://hdl.handle.net/10950/5069