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. Author manuscript; available in PMC: 2013 Jun 11.
Published in final edited form as: Microvasc Res. 2010 Dec 10;81(2):189–197. doi: 10.1016/j.mvr.2010.11.010

Figure 7. Cartoon schematic of proposed HMGB1 pathway leading to paracellular gap formation and endothelial barrier disruption.

Figure 7

HMGB1 induces EC barrier disruption via ligation of the RAGE receptor, resulting in downstream activation of p38 MAP kinase and MAPKAPK-2, and phosphorylation of the actin-binding protein Hsp27. While RAGE is clearly involved in the functional effect of HMGB1 on TER and paracellular gap formation, TLR2 and TLR4 may also be involved in mediating Hsp27 phosphorylation induced by HMGB1 via mechanisms not yet investigated.