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Wnt16 is expressed in bone and arteries, and maintains bone mass in mice and humans, but its role in cardiovascular physiology is unknown. We show that Wnt16 protein accumulates in murine and human vascular smooth muscle (VSM). WNT16 genotypes that convey risk for bone frailty also convey risk for cardiovascular events in the Dallas Heart Study. Murine Wnt16 deficiency, which causes postnatal bone loss, also reduced systolic blood pressure. Electron microscopy demonstrated abnormal VSM mitochondrial morphology in Wnt16-null mice, with reductions in mitochondrial respiration. Following angiotensin-II (AngII) infusion, thoracic ascending aorta (TAA) dilatation was greater in Wnt16-/- vs Wnt16+/+ mice (LDLR-/- background). Acta2 (vascular smooth muscle alpha actin) deficiency has been shown to impair contractile phenotype and worsen TAA aneurysm with concomitant reductions in blood pressure. Wnt16 deficiency reduced expression of Acta2, SM22 (transgelin), and other contractile genes, and reduced VSM contraction induced by TGFβ. Acta2 and SM22 proteins were reduced in Wnt16-/- VSM as was Ankrd1, a prototypic contractile target of Yap1 and Taz activation via TEA domain (TEAD)-directed transcription. Wnt16-/- VSM exhibited reduced nuclear Taz and Yap1 protein accumulation. SiRNA targeting Wnt16 or Taz, but not Yap1, phenocopied Wnt16 deficiency, and Taz siRNA inhibited contractile gene upregulation by Wnt16. Wnt16 incubation stimulated mitochondrial respiration and contraction (reversed by verteporfin, a Yap/Taz inhibitor). SiRNA targeting Taz inhibitors Ccm2 and Lats1/2 mimicked Wnt16 treatment. Wnt16 stimulated Taz binding to Acta2 chromatin and H3K4me3 methylation. TEAD cognates in the Acta2 promoter conveyed transcriptional responses to Wnt16 and Taz. Wnt16 regulates cardiovascular physiology and VSM contractile phenotype, mediated via Taz signaling.
Pubmed ID: 38123514
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This polyclonal targets Wnt16
View all literature mentionsThis monoclonal targets CD31/PECAM1
View all literature mentionsThis monoclonal targets Actin, α-Smooth Muscle
View all literature mentionsThis polyclonal targets smooth muscle actin
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis polyclonal targets H3K4me3
View all literature mentionsThis polyclonal targets RPS21
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis polyclonal targets VCL
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets TAZ
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets IgG H&L
View all literature mentionsThis monoclonal targets Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp362 of human TAZ protein
View all literature mentionsThis polyclonal targets TAGLN/Transgelin
View all literature mentionsThis unknown targets Aldosterone
View all literature mentionsThis polyclonal targets H3K27me3
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis polyclonal targets Wnt16
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsMus musculus with name C57BL/6N-Atm1Brd Wnt16tm2a(EUCOMM)Wtsi/Mmucd from MMRRC.
View all literature mentionsThis monoclonal targets Actin, α-Smooth Muscle
View all literature mentionsThis polyclonal targets smooth muscle actin
View all literature mentionsThis monoclonal targets Actin alpha-Smooth Muscle - Cy3(TM) antibody produced in mouse
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets RPS21
View all literature mentionsThis monoclonal targets CD31/PECAM1
View all literature mentionsThis monoclonal targets Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Asp362 of human TAZ protein
View all literature mentionsThis polyclonal targets H3K4me3
View all literature mentionsThis polyclonal targets VCL
View all literature mentionsThis polyclonal targets TAGLN/Transgelin
View all literature mentionsThis monoclonal targets TAZ
View all literature mentionsThis polyclonal targets Wnt16
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsMus musculus with name C57BL/6N-Atm1Brd Wnt16tm2a(EUCOMM)Wtsi/Mmucd from MMRRC.
View all literature mentionsThis polyclonal targets IgG H&L
View all literature mentionsThis polyclonal targets H3K27me3
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis polyclonal targets Wnt16
View all literature mentionsThis unknown targets Aldosterone
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG H&L
View all literature mentions