Epithelial-Mesenchymal Transition in Idiopathic Pulmonary Fibrosis: A Dynamic Process with Impending Therapeutic Strategies

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with an undefined etiology. This ailment leads to persistent fibrotic scarring of the lung, resulting in interstitial pneumonia, impaired lung function, and death. Recurrent damage to type II alveolar epithelial cells (AECs-II) initiates an abnormal cellular response that activates signaling pathways, leading to epithelial cells undergoing epithelial-mesenchymal transition (EMT). This process entails the loss of epithelial properties and the gain of mesenchymal features, which encompass an improved ability for migration and augmented production of the extracellular matrix. The modified cells, in conjunction with other signaling factors, can recruit and activate fibroblasts, which subsequently differentiate into myofibroblasts that are responsible for collagen production. This results in the thickening and remodeling of lung tissue, disrupting normal lung architecture and contributing to respiratory failure. This review highlights the significance of apoptosis and senescence in AEC-II in promoting EMT, the pathogenesis related to EMT in pulmonary fibrosis (PF), the signaling pathways that activate EMT, and the advanced therapeutic approaches designed to address EMT in IPF. The objective was to enhance the understanding of the pathogenic mechanisms associated with IPF and to establish a foundation for the formulation of more effective therapeutic strategies to mitigate this condition, thus facilitating ongoing research and clinical practices in this domain.