Khondoker M. Akram
Alveolar epithelial cells in idiopathic pulmonary fibrosis display upregulation of TRAIL, DR4 and DR5 expression with simultaneous preferential over-expression of pro-apoptotic marker p53.
Akram, Khondoker M.; Lomas, Nicola J.; Forsyth, Nicholas R.; Spiteri, Monica A
Authors
Nicola J. Lomas
Nicholas R. Forsyth
Monica A Spiteri
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and fatal lung disease of unknown aetiology with no current cure. The pathogenesis of IPF remains unclear but repeated alveolar epithelial cell (AEC) injuries and subsequent apoptosis are believed to be among the initiating/ongoing triggers. However, the precise mechanism of apoptotic induction is hitherto elusive. In this study, we investigated expression of a panel of pro-apoptotic and cell cycle regulatory proteins in 21 IPF and 19 control lung tissue samples. We reveal significant upregulation of the apoptosis-inducing ligand TRAIL and its cognate receptors DR4 and DR5 in AEC within active lesions of IPF lungs. This upregulation was accompanied by pro-apoptotic protein p53 overexpression. In contrast, myofibroblasts within the fibroblastic foci of IPF lungs exhibited high TRAIL, DR4 and DR5 expression but negligible p53 expression. Similarly, p53 expression was absent or negligible in IPF and control alveolar macrophages and lymphocytes. No significant differences in TRAIL expression were noted in these cell types between IPF and control lungs. However, DR4 and DR5 upregulation was detected in IPF alveolar macrophages and lymphocytes. The marker of cellular senescence p21WAF1 was upregulated within affected AEC in IPF lungs. Cell cycle regulatory proteins Cyclin D1 and SOCS3 were significantly enhanced in AEC within the remodelled fibrotic areas of IPF lungs but expression was negligible in myofibroblasts. Taken together these findings suggest that, within the remodelled fibrotic areas of IPF, AEC can display markers associated with proliferation, senescence, and apoptotosis, where TRAIL could drive the apoptotic response. Clear understanding of disease processes and identification of therapeutic targets will direct us to develop effective therapies for IPF.
Citation
Akram, K. M., Lomas, N. J., Forsyth, N. R., & Spiteri, M. A. (2014). Alveolar epithelial cells in idiopathic pulmonary fibrosis display upregulation of TRAIL, DR4 and DR5 expression with simultaneous preferential over-expression of pro-apoptotic marker p53. International Journal of Clinical and Experimental Pathology, 7(2), 552-564
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 10, 2014 |
Online Publication Date | Jan 15, 2014 |
Publication Date | Feb 1, 2014 |
Deposit Date | Jun 7, 2023 |
Journal | International Journal of Clinical and Experimental Pathology |
Publisher | e-Century Publishing |
Peer Reviewed | Peer Reviewed |
Volume | 7 |
Issue | 2 |
Pages | 552-564 |
Keywords | Idiopathic pulmonary fibrosis; TRAIL; DR4; DR5; immunohistochemistry; p53; p21WAF1 |
Publisher URL | https://e-century.us/web/journal_toc.php?journal=ijcep&volume=7&number=2 |
Additional Information | Extra information on this article can be found on the following links; https://e-century.us/files/ijcep/7/2/ijcep1312059.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925899/ |
You might also like
Human Mesenchymal Stem Cell Secretome Driven T Cell Immunomodulation Is IL-10 Dependent
(2022)
Journal Article
Decellularised Pleural Membrane Patches In Pulmonary Regenerative Medicine
(2022)
Conference Proceeding
Stem cell-based therapy for human diseases.
(2022)
Journal Article
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search