Nuclear export by COPS5/CSN5/JAB1 mediates vascular smooth muscle cell dedifferentiation in neointimal hyperplasia - PubMed
5 hours ago
- #vascular smooth muscle cells
- #neointimal hyperplasia
- #COPS5
- COPS5/CSN5/JAB1 plays a role in vascular smooth muscle cell (VSMC) dedifferentiation in neointimal hyperplasia (NH).
- COPS5 levels are increased in human idiopathic pulmonary hypertension (IPAH) neointima and atherosclerotic lesions.
- Smooth muscle-restricted COPS5 knockout (COPS5-SMKO) inhibits VSMC dedifferentiation, proliferation, and NH in mice.
- COPS8 hypomorphism leads to increased COPS5/CSN5 mini-complexes, exacerbating NH and VSMC dedifferentiation.
- Inhibiting COPS5 nuclear export suppresses VSMC dedifferentiation and hyperproliferation, restoring nuclear TP53/p53 and CDKN1B/p27.
- COPS5 deneddylase activity is not required for VSMC dedifferentiation but is crucial for proliferation.
- Overexpression of wild-type COPS5 promotes nuclear export of TP53/p53 and increases nuclear KLF4, enhancing VSMC dedifferentiation.
- Vessel injury upregulates COPS5/CSN5, with nuclear export by COPS5/CSN5 minicomplexes mediating VSMC dedifferentiation.