Hypoxia Inducible Factor-1α in Pulmonary Fibrosis: A Promising Therapeutic Target

Pulmonary fibrosis (PF) is a chronic and progressive disease depicted by excessive scarring, which leads to increased tissue stiffness and loss of lung function. The condition is caused by small injuries to the alveolar epithelium, consequential in the formation of fibroblasts, myofibroblasts, and fibroblastic foci areas within the lung tissue. These cells deposit an excessive amount of collagen-rich extracellular matrix (ECM). Hypoxia, along with its transcription factor known as hypoxia-inducible factor-1 alpha (HIF-1α), activates various signaling pathways that can promote to the progression of PF by promoting myofibroblast differentiation and ECM accumulation. HIF-1α plays a significant role in sustaining inflammatory lung micro-injury, stimulating growth factors, and contributing to PF pathogenesis. Therefore, targeting HIF-1α could be a promising approach to inhibit the progression of PF. This review article discusses the various signaling pathways, excessive ECM formation, and related growth factors involved in HIF-1α regulation in PF, as well as explores the potential use of HIF-1α inhibitors to mitigate PF.