3 research outputs found
Canonical WNT Signaling Pathway is Altered in Mesenchymal Stromal Cells From Acute Myeloid Leukemia Patients And Is Implicated in BMP4 Down-Regulation
Mesenchymal stromal cells (hMSCs) are key components of the bone marrow microenvironment (BMM). A molecular signature in hMSCs from Acute myeloid leukemia patients (hMSC-AML) has been proposed where BMP4 is decreased and could be regulated by WNT signaling pathway. Therefore, the aim of this work was to verify whether the WNT signaling pathway can regulate the BMP4 gene in hMSCs. The results showed differentially expressed genes in the WNT canonical pathway between hMSC-AML and hMSCs from healthy donors and a real-time quantitative assay corroborated with these findings. Moreover, the main WNT canonical pathway regulators were decreased in hMSC-AML, such as LEF-1, β-catenin and the β-catenin/TCF-LEF regulatory complex in the nucleus. This result, together with functional assays, suggests that the induction of BMP4 expression by the WNT signaling pathway is decreased in hMSC-AML. Overall, the WNT canonical pathway is able to regulate the BMP4 gene in hMSC-AML and its reduced activation could also lead to the lower expression of BMP4 in hMSC-AML. Due to the important role of the BMM, changes in BMP4 expression through the WNT canonical pathway may be a potential mechanism of leukemogenesis
Unfractionated Heparin and New Heparin Analogues from Ascidians (Chordate-Tunicate) Ameliorate Colitis in Rats*
The anti-inflammatory effect of mammalian heparin analogues, named dermatan
sulfate and heparin, isolated from the ascidian Styela plicata was
accessed in a TNBS-induced colitis model in rats. Subcutaneous administration
of the invertebrate compounds during a 7-day period drastically reduced
inflammation as observed by the normalization of the macroscopic and
histological characteristics of the colon. At the molecular level, a decrease
in the production of TNF-α, TGF-β, and VEGF was observed, as well
as a reduction of NF-κB and MAPK kinase activation. At the cellular
level, the heparin analogues attenuated lymphocyte and macrophage recruitment
and epithelial cell apoptosis. A drastic reduction in collagen-mediated
fibrosis was also observed. No hemorrhagic events were observed after glycan
treatment. These results strongly indicate the potential therapeutic use of
these compounds for the treatment of colonic inflammation with a lower risk of
hemorrhage when compared with mammalian heparin