SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis. Angiogenesis 2021 May;24(2):387-398
Date
03/30/2021Pubmed ID
33779885Pubmed Central ID
PMC8206051DOI
10.1007/s10456-021-09777-7Scopus ID
2-s2.0-85103389683 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Fluid shear stress provided by blood flow instigates a transition from active blood vessel network expansion during development, to vascular homeostasis and quiescence that is important for mature blood vessel function. Here we show that SMAD6 is required for endothelial cell flow-mediated responses leading to maintenance of vascular homeostasis. Concomitant manipulation of the mechanosensor Notch1 pathway and SMAD6 expression levels revealed that SMAD6 functions downstream of ligand-induced Notch signaling and transcription regulation. Mechanistically, full-length SMAD6 protein was needed to rescue Notch loss-induced flow misalignment. Endothelial cells depleted for SMAD6 had defective barrier function accompanied by upregulation of proliferation-associated genes and down regulation of junction-associated genes. The vascular protocadherin PCDH12 was upregulated by SMAD6 and required for proper flow-mediated endothelial cell alignment, placing it downstream of SMAD6. Thus, SMAD6 is a required transducer of flow-mediated signaling inputs downstream of Notch1 and upstream of PCDH12, as vessels transition from an angiogenic phenotype to maintenance of a homeostatic phenotype.
Author List
Ruter DL, Liu Z, Ngo KM, X S, Marvin A, Buglak DB, Kidder EJ, Bautch VLAuthor
Ziqing Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood CirculationGene Expression Regulation
Homeostasis
Human Umbilical Vein Endothelial Cells
Humans
Mechanotransduction, Cellular
Receptor, Notch1
Shear Strength
Smad6 Protein
