Table 2 Regulators of claudin-5 expression
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 |