Inactivating mutations in Drosha mediate vascular abnormalities similar to hereditary hemorrhagic telangiectasia.

ABSTRACT: The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-β or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-β and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages. Exome sequencing of HHT patients who lacked known pathogenic mutations revealed an overrepresentation of rare nonsynonymous

SUBMITTER: Jiang X 

PROVIDER: S-EPMC5811261 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature