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Gouda, M. ; Rex, D.A.B.* ; Priya, S.E.S.* ; Modi, P.K.* ; Chanderasekaran, J.* ; Bhandary, Y.P.*

Proteomics analysis revealed the importance of inflammation mediated downstream pathways and the protective role of curcumin during bleomycin-induced pulmonary fibrosis in C57BL/6 mice.

J. Proteome Res. 19, 2950-2963 (2020)

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Open Access Green as soon as Postprint is submitted to ZB.

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Bleomycin (BLM)-induced pulmonary fibrosis is characterized by inflammation in the alveoli, subsequent deposition of extracellular matrix (ECM) and myofibroblasts, and an impaired fibrinolytic system. Here, we describe major hematological changes, the IL-17A-mediated p53-fibrinolytic pathway, and the high throughput hits of liquid chromatography-mass spectrometry (LC-MS) analysis during the progression of pulmonary fibrosis and the therapeutic potential of curcumin against disease progression. C57BL/6 mice were exposed to BLM, followed by curcumin intervention after 24 and 48 h. Mice were sacrificed after 7 days to validate the hematological parameters, molecular pathways, and proteomics. Various techniques such as western blotting, immunofluorescence, reverse transcriptase polymerase chain reaction (RT-PCR), hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry were used to validate the proposed theory. LC-MS analysis was performed using a Q-Orbitrap mass spectrometer. The Schrodinger approach was used to perform the in silico molecular docking studies. BLM-exposed mice exhibited gradual weight loss and altered lung morphology; however, these were reversed by curcumin treatment. Significant changes in the hematological parameters confirmed the severity of BLM exposure in the mice, and expression of IL-17A-mediated p53-fibrinolytic system components and alveolar epithelial cell (AEC) apoptosis further confirmed the pathophysiology of pulmonary fibrosis. Differentially expressed proteins were characterized and mapped using the proteomics approach. A strong interaction of curcumin is observed with p53, uPA, and PAI-I proteins. The key role of IL-17A-mediated inflammation in the impairment of the p53-fibrinolytic system and AEC apoptosis was confirmed during BLM-induced pulmonary fibrosis. Therapeutic efficacy of curcumin exhibited a protective role against the progression of pulmonary fibrosis, which promises potent therapeutic modality to target the IL-17A-mediated p53-fibrinolytic system during pulmonary fibrosis.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Pulmonary Fibrosis ; Bleomycin (blm) ; Curcumin ; Il-17a ; P53 ; Pai-1 ; Apoptosis ; Proteomics ; Molecular Docking; Epithelial-cell Apoptosis; Lung Injury; T-cells; Expression; Urokinase; Airway; Edema

ISSN (print) / ISBN 1535-3893

e-ISSN 1535-3907

Journal Journal of Proteome Research

Quellenangaben Volume: 19, Issue: 8, Pages: 2950-2963

Publisher American Chemical Society (ACS)

Publishing Place 1155 16th St, Nw, Washington, Dc 20036 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Lung Health and Immunity (LHI)

Grants Indian Council of Medical Research (ICMR)