YAP1 and TAZ negatively control bone angiogenesis by limiting hypoxia-inducible factor signaling in endothelial cells

Cited 9 time in webofscience Cited 0 time in scopus
  • Hit : 229
  • Download : 8
Blood vessels are integrated into different organ environments with distinct properties and physiology (Augustin and Koh, 2017). A striking example of organ-specific specialization is the bone vasculature where certain molecular signals yield the opposite effect as in other tissues (Glomski et al. 2011; Kusumbe et al., 2014; Ramasamy et al., 2014). Here, we show that the transcriptional coregulators Yap1 and Taz, components of the Hippo pathway, suppress vascular growth in the hypoxic microenvironment of bone, in contrast to their pro-angiogenic role in other organs. Likewise, the kinase Lats2, which limits Yap1/Taz activity, is essential for bone angiogenesis but dispensable in organs with lower levels of hypoxia. With mouse genetics, RNA sequencing, biochemistry, and cell culture experiments, we show that Yap1/Taz constrain hypoxia-inducible factor 1 alpha (HIF1 alpha) target gene expression in vivo and in vitro. We propose that crosstalk between Yap1/Taz and HIF1 alpha controls angiogenesis depending on the level of tissue hypoxia, resulting in organ-specific biological responses.
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
Issue Date
2020-01
Language
English
Article Type
Article
Citation

ELIFE, v.9

ISSN
2050-084X
DOI
10.7554/eLife.50770
URI
http://hdl.handle.net/10203/272246
Appears in Collection
MSE-Journal Papers(저널논문)
Files in This Item
000508545900001.pdf(13.65 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 9 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0