Research ArticleCEREBRAL CAVERNOUS MALFORMATION

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation

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Science Translational Medicine  27 Nov 2019:
Vol. 11, Issue 520, eaaw3521
DOI: 10.1126/scitranslmed.aaw3521

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Two effects in one gene

Cerebral cavernous malformation (CCM) is a genetic vascular disease affecting mainly the brain. Different genes can cause CCM and mutations in PDCD10 are responsible for a particularly severe form of the disease. Now, Tang et al. show that modulation of the gut barrier could explain the poor prognosis of patients with PDCD10 mutations. In mice, Pdcd10 deletion specifically in the gut epithelium disrupted the colonic mucosal barrier and increased CCM formation. Pharmacologic experiments targeting the glucocorticoid system demonstrated that both brain endothelial cells and gut epithelial cells contribute to CCM formation, suggesting that therapies targeting either brain or gut signaling could be effective for treating CCM.

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