Metabolic Targeting of Fibrotic Diseases
Glycolytic reprogramming in myofibroblast differentiation and fibrotic disease progression
Pulmonary fibrosis, scarring of the lungs caused by many conditions such as infections, environmental agents, and certain medications, is a ultimately fatal progressive disease with not only limited treatment options but also a poor prognosis and a survival expectancy of less than five years. Furthermore, idiopathic pulmonary fibrosis, the most common form of the disease, has no known cause. Therefore, it is crucial that mechanisms underlying pulmonary fibrosis progression be elucidated.
The presence of myofibroblasts in the animal models of pulmonary fibrosis as well as patients with lung fibrosis has been well documented in the current literature. Furthermore, myofibroblasts, which are responsible for the deposition of the matrix that constitutes the scar, have been found to play integral roles in the pathogenesis of this disease. During fibrotic progression, myofibroblast differentiation of pulmonary fibroblasts is a major process that facilitates the progression, migration, and secretion of extracellular matrix and collagen. In my lab, we are currently investigating the glycolytic reprogramming of fibroblasts that is crucial in fibroblast to myofibroblast differentiation utilizing in vitro culture as well as animal models in order to identify novel therapeutic targets.
Utilizing mouse models of pulmonary fibrosis, we are investigating the effects of metabolic targeting on disease progression. This image shows elevated collagen accumulation (pink) characteristic of a fibrotic lung.