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Table 2 Regulators of claudin-5 expression

From: Claudin-5: gatekeeper of neurological function

Regulators Effect on expression Mechanism
Phosphorylation Decrease Thr207 PKA/PKC signalling
VEGF Decrease Basolateral VEGFR2-induced downregulation via p38
TGF-β Decrease ALK signalling/MMP upregulation
GDNF Increase
Adrenomedullin Increase
Glucocorticoid Increase promoter activity Glucocorticoid response elements in claudin-5 promoter
SOX-18 Increase promoter activity SOX binding in claudin-5 promoter transactivate claudin-5
TNFα Decrease NFκB dependent repression
Estrogen Increase Estrogen receptor/SP1 binding in claudin-5 promoter
MMP Degradation
Fox01 Repress transcription Nuclear accumulation and repression of claudin-5 transcription
cAMP Increase cell–cell localisation PKA-dependent and independent pathways
SHH Increase SHH binding to patched releases inhibitory effect of Gli on downstream targets including claudin-5
VE-cadherin Increase Prevent Fox01/β-catenin mediated repression
Ubiquitination Degradation Ubiquitination at L1999. Proteosome-mediated degradation
CCL2 Turnover Caveolin-dependent removal
Glutamate Decrease NMDAR-mediated-cPLA2 activation and MMP upregulation
Autophagosome Turnover ECL2-dependent endocytosis