Functional Repercussions of Hypoxia-Inducible Factor-2 alpha in Idiopathic Pulmonary Fibrosis

Hypoxia and hypoxia-inducible factors (HIFs) are essential in regulating several cellular processes, such as survival, differentiation, and the cell cycle; this adaptation is orchestrated in a complex way. In this review, we focused on the impact of hypoxia in the physiopathology of idiopathic pulmonary fibrosis (IPF) related to lung development, regeneration, and repair. There is robust evidence that the responses of HIF-1 alpha and -2 alpha differ; HIF-1 alpha participates mainly in the acute phase of the response to hypoxia, and HIF-2 alpha in the chronic phase. The analysis of their structure and of different studies showed a high specificity according to the tissue and the process involved. We propose that hypoxia-inducible transcription factor 2a (HIF-2 alpha) is part of the persistent aberrant regeneration associated with developing IPF.