Medicine in Drug Discovery (Dec 2023)
Idiopathic pulmonary fibrosis: Pathophysiology, cellular signaling, diagnostic and therapeutic approaches
Abstract
Idiopathic pulmonary fibrosis (IPF) is a life-threatening and progressive interstitial lung disease. Healthy pulmonary tissues were replaced by an altered extracellular matrix (ECM) and destroyed the alveolar architecture, which led to the disruption of gas exchange, decreased lung compliance, and ultimately led to the failure of respiration and death. IPF is associated with dyspnoea and cough, eventually impairing the quality of a large population worldwide, with the incidence rate increasing drastically with age. The IPF involves a complex pathophysiology; thus, it is necessary to understand the precise molecular mechanism for lung fibrosis to develop novel therapeutic options. Different kinases, including p38 mitogen-activated protein kinase, JNK (c-Jun N-terminal kinase), and SAPKs (Stress-activated protein kinases), were ubiquitously expressed in numerous variety of cells and were activated in response to inflammatory stimuli, cellular environmental stress, and stimuli for apoptosis. After many failed drugs for IPF in clinical trials, two drugs, namely nintedanib and pirfenidone, were approved, which helped to slow the disease progression. However, the prognosis of IPF remains poor, which leads to continuing the search for better drugs, targeting to either reduce or halt the disease progression. The current review summarises the pathophysiology, signaling, and role of different kinases, therapeutic interventions, investigational therapies, and biomarkers for IPF. A better understanding of the pathophysiology of IPF will be helpful to understand disease mechanisms, discovering potential biomarkers, and development of effective therapeutics to handle patients.