Graduation Year
2022
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Narasaiah Kolliputi, Ph.D.
Committee Member
Robert Deschenes, Ph.D.
Committee Member
Hana Totary-Jain, Ph.D.
Committee Member
Javier Cuevas, Ph.D.
Committee Member
Thomas Taylor-Clark, Ph.D.
Committee Member
Bala Chandran, Ph.D.
Keywords
Energy, Mitophagy, ARDS, Hyperoxia, Mitochondria
Abstract
Acute Lung Injury (ALI) is a set of signs and symptoms that lead to acute hypoxemic respiratory failure characterized by bilateral pulmonary infiltrates not attributed to cardiogenic origin. It is caused by a massive innate immune response, with the migration of white blood cells (neutrophils and macrophages principally) and a cytokine storm, followed by alterations in mitochondrial function, increase in reactive oxygen species production, and oxidative stress that in turn induces more mitochondrial damage. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI and reducing mitochondrial dysfunction could be a possible target in the treatment of the disease. Some investigators have determined that BMI1 has a role in mitochondrial function, but its role is unclear, and the metabolic pathway through which BMI1 regulates mitochondrial function and oxidative stress has not been established. This study shows that BMI1 plays a pivotal role in mitochondrial function during hyperoxia-induced ALI (HALI) in vitro and in vivo, and BMI1 silencing, or depletion induces mitophagy and reduces cell survival by blocking the PI3K pathway mediated by PTEN increases, decreasing the ability of lung cells to produce ATP and to consume oxygen, resulting in the use of glycolysis as an energy source. In vivo, the depletion of BMI1 decreases lung compliance, increases elastance, and induces deleterious lung damage in mice, leading to worsening of HALI. This research describes BMI1 as a possible therapeutic target in treating of ALI/ARDS.
Scholar Commons Citation
Hernández-Cuervo, María Helena, "Role of BMI1 in Acute Lung Injury" (2022). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/9373
