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TAK1 signaling is a potential therapeutic target for pathological angiogenesis

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Abstract

Angiogenesis plays a critical role in both physiological responses and disease pathogenesis. Excessive angiogenesis can promote neoplastic diseases and retinopathies, while inadequate angiogenesis can lead to aberrant perfusion and impaired wound healing. Transforming growth factor β activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is a key modulator involved in a range of cellular functions including the immune responses, cell survival and death. TAK1 is activated in response to various stimuli such as proinflammatory cytokines, hypoxia, and oxidative stress. Emerging evidence has recently suggested that TAK1 is intimately involved in angiogenesis and mediates pathogenic processes related to angiogenesis. Several detailed mechanisms by which TAK1 regulates pathological angiogenesis have been clarified, and potential therapeutics targeting TAK1 have emerged. In this review, we summarize recent studies of TAK1 in angiogenesis and discuss the crosstalk between TAK1 and signaling pathways involved in pathological angiogenesis. We also discuss the approaches for selectively targeting TAK1 and highlight the rationales of therapeutic strategies based on TAK1 inhibition for the treatment of pathological angiogenesis.

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Acknowledgements

The authors thank Ms Jessika Hernandez Garcia for assistance with figure illustrations. This work was supported by grants from the National Health and Medical Research Council of Australia (1185600) and the National Natural Science Foundation of China (82000902). The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government.

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  1. Linxin Zhu and Suraj Lama have contributed equally to this work as first author.

  2. Jiang-Hui Wang and Guei-Sheung Liu have contributed equally to this work.

Authors and Affiliations

  1. Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia

    Linxin Zhu, Suraj Lama & Guei-Sheung Liu

  2. Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China

    Linxin Zhu & Leilei Tu

  3. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia

    Gregory J. Dusting & Jiang-Hui Wang

  4. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia

    Gregory J. Dusting & Guei-Sheung Liu

  5. Aier Eye Institute, Changsha, Hunan, China

    Guei-Sheung Liu

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Conceptualization- LZ, SL, J-HW, G-SL Writing (Original Draft)- LZ, SL, J-HW, G-SL Writing (Review & Editing)- LT, GJD Project Administration- J-HW, G-SL Funding Acquisition- LT, G-SL Project Supervision- G-SL.

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Zhu, L., Lama, S., Tu, L. et al. TAK1 signaling is a potential therapeutic target for pathological angiogenesis. Angiogenesis 24, 453–470 (2021). https://doi.org/10.1007/s10456-021-09787-5

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