SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis
| Autor: | Allison Marvin, Ziqing Liu, Shaka X, Elise J. Kidder, Danielle B. Buglak, Kimlynn M. Ngo, Victoria L. Bautch, Dana L Ruter |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Notch Smad6 Protein Physiology Angiogenesis Endothelial cells Clinical Biochemistry Notch signaling pathway PCDH12 SMAD Brief Communication Mechanotransduction Cellular 03 medical and health sciences 0302 clinical medicine Blood vessels Downregulation and upregulation Human Umbilical Vein Endothelial Cells medicine BMP Homeostasis Humans Receptor Notch1 Barrier function Chemistry Blood flow Protocadherins Cell biology Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Blood Circulation Shear Strength 030217 neurology & neurosurgery Blood vessel |
| Zdroj: | Angiogenesis |
| ISSN: | 1573-7209 0969-6970 |
| DOI: | 10.1007/s10456-021-09777-7 |
| Popis: | 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. Supplementary Information The online version contains supplementary material available at 10.1007/s10456-021-09777-7. |
| Databáze: | OpenAIRE |
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