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. Author manuscript; available in PMC: 2022 Sep 22.
Published in final edited form as: Genes Dis. 2022 Nov;9(6):1594–1607. doi: 10.1016/j.gendis.2021.09.008

Table 1. Evidence of altered autophagy in IPF.

Protein Change Model Reference
p62 Increased (protein) in IPF vs. control. IHC of IPF vs. normal lung Hill et al (2019)44
Increased in IPF vs. control. IF of IPF vs. Control Patel et al (2012)38

  • Only ATII cells express p62 in normal lung. In IPF lungs, p62 was also expressed in ATII cells in ‘normal’ areas without distortion.

  • p62 was strongly expressed by metaplastic epithelial cells (including cuboidal squamous and bronchiolar-type cells) These cells had some distortion. In areas of dense fibrosis with remodeling, lower expression was observed in honeycomb regions in sub-epithelial fibroblasts,

  • Staining was also demonstrated in sub-epithelial fibroblasts.

 IHC IPF vs. normal lung Araya et al (2013)37
Ubiquitin

  • No expression detected in normal lungs.

  • ATII cells of ‘normal’ areas of IPF lungs have some staining.

  • In areas of fibrosis, ubiquitin staining correlated with p62 staining in both ATII cells and fibroblasts.

  • In honeycomb regions, epithelial and fibroblasts expressed ubiquitinated proteins.

 IHC IPF vs. normal lung Araya et al (2013)37
Autophagosomes (visualised by EM): reduced compared to both control and COPD patients. Electron microscopy Patel et al (2012)38
LC3 Dot-like staining of LC3 (resembles autophagosomes) found in ATII cells cytoplasm in the ‘normal’ regions of IPF lung without distortion. However, not in ATII cells of normal lung (confirmed by co-staining for Prosurfactant Protein C). No further staining observed, irrespective of the degree of the fibrosis. Human IPF tissue Araya et al (2013)37
LC3B reduced in IPF compared to adjacent normal tissue. Human IPF tissue Wang et al (2018)47
LC3-II reduced in IPF vs. transplant patients without IPF. Whole lung homogenate Patel et al (2012)38
Beclin-1 Highly diffuse cytoplasmic staining in normal and IPF lung. Cytoplasm of ATII cells in normal areas of IPF lungs had higher expression than epithelial cells in other lesions. IHC IPF vs. normal lung Araya et al (2013)37
Decreased in IPF. IHC human tissue and primary fibroblasts Ricci et al (2013)43
Atg4b

  • Not detectable in healthy tissue.

  • In IPF lungs, mainly localised to ATII cells typically overlapping FF and hyperplastic epithelial cells, non-ciliated columnar cells and bronchiolar epithelial cells.

  • Some staining in a few interstitial inflammatory cells was observed.

  • No staining in fibroblasts.

 Human IPF tissue Cabrera et al (2015)48
p-S6 Upregulated in IPF tissue. IPF lung tissue compared to healthy lung tissue Gui et al (2015)49
pAMPK Increased in IPF vs. control. Immunoblot IPF lungs Patel et al (2012)38