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. 2020 Sep 18;8:567682. doi: 10.3389/fcell.2020.567682

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Copyright © 2020 Zhang and Yang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Dysregulation of TGF-β/BMP signaling in CCM. Mutant CCM release the inhibition of MEEK3/ERK pathway, which trigger the expression of KLF2/4. KLF2/4 subsequently suppress the expression of endothelial markers and induce the expression of EndMT-related molecules. KLF4 could also transcriptionally upregulate BMP6 to active TGF-β/BMP cascades in ECs. Besides, activation of TLR4 associated with CD14 by Gram-negative bacteria and lipopolysaccharide injection could increase the expression of Klf2/4 and promote CCM formation.