Casein kinase 1δ/ε inhibitor, PF670462 attenuates the fibrogenic effects of transforming growth factor-β in pulmonary fibrosis

CR Keenan; SY Langenbach; F Jativa; T Harris; M Li; Q Chen; Y Xia; B Gao; MJ Schuliga; J Jaffar; D Prodanovic; Y Tu; A Berhan; PVS Lee; GP Westall; AG Stewart

Journal article

Casein kinase 1δ/ε inhibitor, PF670462 attenuates the fibrogenic effects of transforming growth factor-β in pulmonary fibrosis

CR Keenan, SY Langenbach, F Jativa, T Harris, M Li, Q Chen, Y Xia, B Gao, MJ Schuliga, J Jaffar, D Prodanovic, Y Tu, A Berhan, PVS Lee, GP Westall, AG Stewart

Frontiers in Pharmacology | FRONTIERS MEDIA SA | Published : 2018

DOI: 10.3389/fphar.2018.00738

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Abstract

Transforming growth factor-beta (TGF-β) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition of TGF-β is limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover a little-known connection between TGF-β signaling and casein kinase (CK) activity. We have examined the abundance of CK1 delta and epsilon (CK1δ/ε) in lung tissue from IPF patients and non-diseased controls, and investigated whether inhibition of CK1δ/ε with PF670462 inhibits pulmonary fibrosis. CK1δ/ε levels in lung tissue from IPF patients and non-diseased controls were assessed by immunohistoche..

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University of Melbourne Researchers

Christine Keenan Author

Meina Li Author

Bryan Gao Author

Peter Lee Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was funded in part by grants from NHMRC (Australia): #1045372; #1137171 and #1059665, and the Australian Research Council LP160100635 and ARC Centre for Personalised Therapeutics Technologies IC170100016 (AS).