David A Skerrett-Byrne1,2,3, Elizabeth G Bromfield2,3,4, Heather C Murray3,5, M Fairuz B Jamaluddin3,5, Andrew G Jarnicki1,6, Michael Fricker1,3, Ama T Essilfie1,7, Bernadette Jones1,3, Tatt J Haw1,3, Daniel Hampsey1,3, Amanda L Anderson2,3, Brett Nixon2,3, Rodney J Scott3,5, Peter A B Wark1,3, Matthew D Dun3,5, Philip M Hansbro1,3,8. 1. Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 2. Pregnancy and Reproduction Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 3. University of Newcastle, Callaghan, New South Wales, Australia. 4. Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. 5. Cancer Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 6. Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia. 7. Queensland Institute of Medical Research, Herston, Queensland, Australia. 8. Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, New South Wales, Australia.
Abstract
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. METHODS: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks. RESULTS: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of human COPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and human COPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred. CONCLUSION: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies.
BACKGROUND AND OBJECTIVE:Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. METHODS: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks. RESULTS: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of humanCOPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and humanCOPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred. CONCLUSION: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies.
Authors: Min Zhang; Riccardo Zenezini Chiozzi; David A Skerrett-Byrne; Tineke Veenendaal; Judith Klumperman; Albert J R Heck; Brett Nixon; J Bernd Helms; Bart M Gadella; Elizabeth G Bromfield Journal: Front Cell Dev Biol Date: 2022-02-18
Authors: Natalie A Trigg; David A Skerrett-Byrne; Jacinta H Martin; Geoffry N De Iuliis; Matthew D Dun; Shaun D Roman; Andrew L Eamens; Brett Nixon Journal: Data Brief Date: 2022-03-08
Authors: Chantal Donovan; Richard Y Kim; Izabela Galvao; Andrew G Jarnicki; Alexandra C Brown; Bernadette Jones-Freeman; Henry M Gomez; Ridhima Wadhwa; Elinor Hortle; Ranjith Jayaraman; Haroon Khan; Sophie Pickles; Priyanka Sahu; Vrushali Chimankar; Xiaofan Tu; Md Khadem Ali; Jemma R Mayall; Duc H Nguyen; Kurtis F Budden; Vinod Kumar; Kate Schroder; Avril Ab Robertson; Matthew A Cooper; Peter Ab Wark; Brian G Oliver; Jay C Horvat; Philip M Hansbro Journal: Immunol Cell Biol Date: 2022-03-21 Impact factor: 5.853