Integrins as a drug target in liver fibrosis

Rahman, Syedia R.; Roper, James A.; Grove, Jane I.; Aithal, Guruprasad P.; Pun, K. Tao; Bennett, Andrew J.

Abstract

As the worldwide prevalence of chronic liver diseases is high and continuing to increase, there is an urgent need for treatment to prevent cirrhosis-related morbidity and mortality. Integrins are heterodimeric cell-surface proteins that are promising targets for therapeutic intervention. αv integrins are central in the development of fibrosis as they activate latent TGFβ, a known profibrogenic cytokine. The αv subunit can form heterodimers with β1, β3, β5, β6 or β8 subunits and one or more of these integrins are central to the development of liver fibrosis, however, their relative importance is not understood. This review summarises the current knowledge of αv integrins and their respective β subunits in different organs, with a focus on liver fibrosis and the emerging preclinical and clinical data with regards to αv integrin inhibitors.

Citation

Rahman, S. R., Roper, J. A., Grove, J. I., Aithal, G. P., Pun, K. T., & Bennett, A. J. (2022). Integrins as a drug target in liver fibrosis. Liver International, 42(3), 507-521. https://doi.org/10.1111/liv.15157

• Journal Article Type: Review
• Acceptance Date: Dec 30, 2021
• Online Publication Date: Jan 20, 2022
• Publication Date: 2022-03
• Deposit Date: Jan 26, 2022
• Publicly Available Date: Jan 21, 2023
• Journal: Liver International
• Print ISSN: 1478-3223
• Electronic ISSN: 1478-3231
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 3
• Pages: 507-521
• DOI: https://doi.org/10.1111/liv.15157
• Keywords: Hepatology
• Public URL: https://nottingham-repository.worktribe.com/output/7340214
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/liv.15157
• Additional Information: This is the peer reviewed version of the following article: Rahman, S.R., Roper, J.A., Grove, J.I., Aithal, G.P., Pun, K.T. and Bennett, A.J. (2022), Integrins as a drug target in liver fibrosis. Liver International. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1111/liv.15157. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.