Search
  • Raymond Wong

New preprint: Novel method to generate neurons using biomaterial and CRISPRa

TAK1 blockade as a therapy for retinal neovascularization

Fan-Li Lin, Jiang-Hui Wang, Jinying Chen, Linxin Zhu, Yu-Fan Chuang, Leilei Tu, Chenkai Ma, Suraj Lama, Damien Ling, Raymond Ching-Bong Wong, Alex Hewitt, Ching-Li Tseng, Bang Bui, Peter van Wijngaarden, Gregory Dusting, Peng-Yuan Wang, Guei-Sheung Liu

biorXiv, https://doi.org/10.1101/2021.01.29.428701



Abstract


Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines. TAK1 is also a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Selective inhibition of TAK1 activation by 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Transcriptome profiling revealed that TAK1 activation in human microvascular endothelial cells under TNFα stimulation led to increase the gene expression related to cytokines and leukocyte-endothelial interaction, mainly through nuclear factor kappa B (NFκB) signaling pathways. These results reveal that inhibition of TAK1 signaling may have therapeutic value for the treatment of pathological angiogenesis in the retina.


Read the paper here.

4 views