Biochemistry, Biophysics, and Structural Biology Commons^™

Glutathionylation/Glutaredoxin Axis And The Regulation Of Epithelial Cell Plasticity And Fibroblast Activation In Airway Fibrosis, Shi Biao Chia

Graduate College Dissertations and Theses

Asthma is a complex lung disorder that affects more than 200 million people across the globe. About 10% of asthmatics have severe disease accompanied by structural airway remodeling, including subepithelial fibrosis, airway smooth muscle cell hyperplasia, goblet metaplasia, and increased vascularization. Oxidative stress has been well-linked to asthma pathogenesis; however, the precise redox mechanisms governing the pathological states are slowly being teased apart in the recent years. Protein S-glutathionylation (PSSG) is a posttranslational modification where a three amino acid-peptide, glutathione, forms a disulfide bond with reactive cysteines of a protein thereby potentially changing the protein’s biological functions. Glutaredoxins are members …

Molecular Characterization Of Purβ: A Purine-Rich Single-Stranded Dna-Binding Repressor Of Myofibroblast Differentiation, Amy Rumora

Graduate College Dissertations and Theses

The trans-differentiation of injury-activated fibroblasts to myofibroblasts is a process that provides contractile strength for wound closure. Persistent myofibroblast differentiation, however, is associated with fibrotic pathologies such as organ fibrosis, vascular remodeling, and atherosclerotic plaque formation. Myofibroblasts acquire a contractile phenotype with biochemical properties characteristic of both smooth muscle cells and stromal fibroblasts. The cyto-contractile protein, smooth muscle α-actin (SMαA) is a biomarker of myofibroblast differentiation. Expression of the SMαA gene, ACTA2, is regulated by cis-acting elements and transcription factors that activate or repress the ACTA2 promoter.

Purine-rich element binding proteins A (Purα) and B (Purβ) are sequence-specific, …