Anti-CTNNB1 (mutation D32N) Monoclonal Antibody, clone XH023

Objective- The Wnt/beta-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/beta-catenin signaling by induced overexpression of Axin1, an inhibitor of beta-catenin signaling, specifically in endothelial cells (Axin1(iEC)-(OE)). AOE (Axin1 overexpression) in Axin1(iEC)-(OE) mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/beta-catenin driven CNS vascular development in zebrafish also suggested that Axin1(iEC)-(OE) led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, beta-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 (Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific beta-catenin-responsive ECM signature was also repressed in Axin1(iEC)-(OE) and endothelial cell-specific beta-catenin-knockout mice (Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/beta-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-beta-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development.

To investigate the specific targets along with the pharmacological action mechanisms of Salvia miltiorrhiza against cardiovascular deseases (CVD). TCMSP and pieces of literature were searched to develop the ingredient-target database for Radix Salvia miltiorrhiza followed by the selection of CVD-related targets. The link between these targets was established by the STITCH database and by designing a network through gene ontology (GO) enrichment analysis, ClueGO and its plugin. As a result of the literature search, 202 chemical constituents and 2566 protein targets of these chemical constituents were enlisted. After careful screening, 41 protein targets were found to have biological activity against CVD. Ultimately, 214 GO terms were found by analysis of gene functional annotation clusters and the abundance value of these targets. The majority of these were linked with CVD. Several numbers of protein targets such as ESR1, CTNNB1, and MAPK14 were served as a functional moiety for Radix Salviae miltiorrhiza to treat CVD. This study aids to perceive the molecular mechanism and the clinical interpretations of Radix Salviae miltiorrhiza in CVD. The following are the signaling mechanisms of The given results aids to perceive the molecular mechanism and the clinical interpretations of Radix Salviae miltiorrhiza such as Histone H3-K9 methylation, DNA damage response signal transduction by p53 class mediator resulting in cell cycle arrest, and embryonic skeletal limb joint morphogenesis signaling pathway.