Insights in Chest Diseases

NADPH oxidase-4: Pathophysiology and therapeutic potential in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of lung disease with unknown etiology that causes scarring and stiffness in the tissue. The disease represents 50% 3-5-year survival post-diagnosis. Mounting evidence indicates that oxidative stress is a significant player in the pathogenesis of IPF. Oxidative stress is characterized by an increase in the production of reactive oxygen species (ROS) sourced predominantly from NADPH oxidases (NOXes) and mitochondria. Several Studies have unveiled the role of NOXes esp NOX1, NOX2 and NOX4 in the IPF pathogenesis in addition to the role of mitochondrial ROS. Among the other NOX-isoforms, NOX4 is particularly noted for its inducibility by transforming growth factor-beta (TGF-β, known for its high levels in IPF) and its ability to generate H₂O₂ after induction. Studies have shown that NOX4 may be an important catalyst in the maintenance of a profibrogenic environment, mainly acting through fibroblasts and extra-cellular matrix (ECM) deposition. As such, several therapeutic strategies have been proposed to reduce the production of ROS and attenuate its role in fibrosis. Some of the most notable modalities aim to selectively target and inhibit NOX4 and its concomitant dynamic interplay with other related signaling molecules in the fibrotic pathway. Many emerging therapeutic options are currently being investigated, however, the search for the ideal specific mode of treatment remains elusive.

Author(s):

Ashish Dhyani

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