Regulation of Macroautophagy in Idiopathic Pulmonary Fibrosis

Introduction: It is currently unknown if lysosome related pathways are altered under conditions of idiopathic pulmonary fibrosis (IPF). Autophagy has been known from several years as a self-eating catabolic pathway, activated mainly to degrade the cell's own unused organelles, macromolecules and long-lived proteins via the lysosomal system. Macroautophagy is a well characterized and one of the important types of autophagy that contributes to lysosomal degradation. It involves sequestration of a double membrane structure called autophagosome, which will finally fuse with the lysosome for degradation of its contents. Here, we studied macroautophagy, an important lysosomal degradation pathway, in IPF.

Methods: Markers of macroautophagy like LC3B, p62 and transcription factor EB (TFEB) were analyzed in IPF and healthy donor lungs by means of both western blotting and immunohistochemistry. Band intensities of exposed western blot films were analyzed by densitometric scanning and quantified using the Alpha EaseFC Imaging System.

Results: LC3B and p62 were found to be unchanged by WB and IHC. However, TFEB was significantly elevated in IPF lungs. Nuclear localization of TFEB within alveolar type II cells was observed in IPF lungs and its overall protein level also increased.

Conclusions: We conclude that macroautophagy is not greatly altered in the lungs of IPF lungs as compared to healthy donors. This could be because of increased TFEB levels, which is known to affect and regulate several autophagy related gene products, thereby promoting autophagy in IPF lungs.