Mitochondrial Transplantation: A Novel Therapy for Lung Fibrosis
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible disease with no effective pharmacotherapeutic treatments. IPF arises from relentless and extensive fibroproliferative injury, which itself stems from the inability of normal repair processes in the lung to deactivate following stimuli. The disease is characterized by focal zones of fibroblast proliferation. Transforming growth factor-Beta (TGF-Beta) plays a crucial role in fibrosis development, mediating cell activation, migration, and invasion. Increased TGF-Beta mediates metabolic reprogramming in cells involved in IPF progression, shifting bioenergetics towards increased glycolysis, and causing mitochondrial dysfunction. In fibroblasts, TGF-Beta increases expression of glycolytic enzymes and glucose transporters, as well as lactate production. In alveolar epithelial cells, genes involved in metabolism are downregulated, and there is increased lactate production. A more glycolytic phenotype is also observed in alveolar macrophages in IPF. Decreased ATP production occurs in fibroblasts, while in IPF alveolar epithelial cells, fibroblasts, and macrophages, decreased electron transport chain (ETC) complex activity and lower oxygen consumption rates (OCR) have been observed. This work aims to deliver polymer-functionalized mitochondria to fibroblasts, alveolar epithelial cells, and macrophages in IPF lungs with the goal of restoring a favorable metabolic phenotypes and mitochondrial function that can attenuate or reverse the disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1177032
Entities
People
- Elvin Blanco
Organizations
- Houston Methodist Research Institute