Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA.
The Molecular Biology Institute at UCLA, Los Angeles, CA 90095-1570, USA.
Int J Mol Sci. 2023 Mar 22;24(6):5971. doi: 10.3390/ijms24065971.
Endothelial-mesenchymal transition (EndMT) drives the endothelium to contribute to vascular calcification in diabetes mellitus. In our previous study, we showed that glycogen synthase kinase-3β (GSK3β) inhibition induces β-catenin and reduces mothers against DPP homolog 1 (SMAD1) to direct osteoblast-like cells toward endothelial lineage, thereby reducing vascular calcification in deficiency. Here, we report that GSK3β inhibition reduces vascular calcification in diabetic mice. Cell lineage tracing reveals that GSK3β inhibition redirects endothelial cell (EC)-derived osteoblast-like cells back to endothelial lineage in the diabetic endothelium of mice. We also find that the alterations in β-catenin and SMAD1 by GSK3β inhibition in the aortic endothelium of diabetic mice are similar to mice. Together, our results suggest that GSK3β inhibition reduces vascular calcification in diabetic arteries through a similar mechanism to that in mice.
内皮-间充质转化（EndMT）促使内皮细胞参与糖尿病中的血管钙化。在我们之前的研究中，我们表明糖原合成酶激酶-3β（GSK3β）抑制诱导β-连环蛋白并减少母系抗 DPP 同源物 1（SMAD1），以直接将成骨样细胞定向为内皮谱系，从而减少 缺乏症中的血管钙化。在这里，我们报告 GSK3β 抑制可减少糖尿病 小鼠的血管钙化。细胞谱系追踪显示，GSK3β 抑制将内皮细胞（EC）衍生的成骨样细胞重新定向回糖尿病 小鼠的内皮中。我们还发现，糖尿病 小鼠主动脉内皮中 GSK3β 抑制引起的β-连环蛋白和 SMAD1 的改变与 小鼠相似。总之，我们的结果表明，GSK3β 抑制通过类似于 小鼠的机制减少糖尿病动脉中的血管钙化。
