Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 May;357(5):374-378.
doi: 10.1016/j.amjms.2019.01.010. Epub 2019 Jan 22.

Epithelial Injury and Dysfunction in the Pathogenesis of Idiopathic PulmonaryFibrosis

Nichelle I Winters  1 , Ankita Burman  2 , Jonathan A Kropski  3 , Timothy S Blackwell  4
Affiliations
Review

Epithelial Injury and Dysfunction in the Pathogenesis of Idiopathic PulmonaryFibrosis

Nichelle I Winters et al. Am J Med Sci. 2019 May.

Abstract

Idiopathic pulmonary fibrosis is a disease of older adults leading to progressive dyspnea and reduced exercise capacity, typically resulting in death within 3-5years of diagnosis. Underlying genetic susceptibility combined with environmental insults is proposed to trigger a chronic wound repair response, leading to activation of the fibrotic cascade. Perturbations in several molecular pathways mediate vulnerability of the alveolar epithelium to injurious agents, including the unfolded protein response, autophagy, mitophagy, and cellular senescence. These cellular responses are intricately intertwined and link genetic susceptibility to the progressive fibrotic phenotype. Ongoing studies investigating these pathways in type II alveolar epithelial cells show promise for identifying new targeted interventions that could prevent or halt the progression of IPF.

Keywords: Autophagy; Endoplasmic reticulum stress; Idiopathic pulmonary fibrosis; Mitophagy; Senescence.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: TSB and JAK have grant funding from Boehringer Ingelheim and TSB has grant funding from Celgene.

Figures

Figure 1.
Figure 1.. Molecular pathways influencing pro-fibrotic phenotypes of type II alveolar epithelial (AT2) cells in IPF.
Genetic and environmental factors converge to regulate pathways that affect the ability of AT2 cells to respond to injury, including ER stress, mitophagy, autophagy, and DNA damage response. Pathological interactions and imbalances between these pathways result in pro-fibrotic phenotypes in AT2 cells, including senescence and apoptosis, which contribute to IPF pathogenesis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cosgrove GP, Brown KK, Schiemann WP, et al. Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Am J Respir Crit Care Med. 2004;170(3):242–251. - PubMed
    1. Cavazza A, Rossi G, Carbonelli C, et al. The role of histology in idiopathic pulmonary fibrosis: an update. Respir Med. 2010;104 Suppl 1:S11–22. - PubMed
    1. Myers JL, Katzenstein AL. Beyond a consensus classification for idiopathic interstitial pneumonias: progress and controversies. Histopathology. 2009;54(1):90–103. - PubMed
    1. Leslie KO. My approach to interstitial lung disease using clinical, radiological and histopathological patterns. J Clin Pathol. 2009;62(5):387–401. - PMC - PubMed
    1. AL K Pathogenesis of “fibrosis” in interstitial pneumonia: an electron microscopic study. Hum Pathol. 1985;16(10):1015–1024. - PubMed

Publication types

MeSH terms