Lu Jia-Qi, Luo Zhi-Yan, Sun Chengyang, Wang Si-Miao, Sun Dixiang, Huang Ruo-Jing, Yang Xuesong, Ding Yong, Wang Guang
The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Division of Histology and Embryology, International Joint Laboratory for Embryonic Development and Prenatal Medicine, School of Medicine, Jinan University, Guangzhou, China.
Front Pharmacol. 2024 Mar 7;15:1295356. doi: 10.3389/fphar.2024.1295356. eCollection 2024.
Hyperglycemia in pregnancy can increase the risk of congenital disorders, but little is known about craniofacial skeleton malformation and its corresponding medication. Our study first used meta-analysis to review the previous findings. Second, baicalin, an antioxidant, was chosen to counteract high glucose-induced craniofacial skeleton malformation. Its effectiveness was then tested by exposing chicken embryos to a combination of high glucose (HG, 50 mM) and 6 μM baicalin. Third, whole-mount immunofluorescence staining and hybridization revealed that baicalin administration could reverse HG-inhibited neural crest cells (NCC) delamination and migration through upregulating the expression of Pax7 and Foxd3, and mitigate the disordered epithelial-mesenchymal transition (EMT) process by regulating corresponding adhesion molecules and transcription factors (i.e., E-cadherin, N-cadherin, Cadherin 6B, Slug and Msx1). Finally, through bioinformatic analysis and cellular thermal shift assay, we identified the AKR1B1 gene as a potential target. In summary, these findings suggest that baicalin could be used as a therapeutic agent for high glucose-induced craniofacial skeleton malformation.
孕期高血糖会增加先天性疾病的风险，但关于颅面骨骼畸形及其相应治疗药物却知之甚少。我们的研究首先采用荟萃分析来回顾先前的研究结果。其次，选择抗氧化剂黄芩苷来对抗高糖诱导的颅面骨骼畸形。然后通过将鸡胚暴露于高糖（HG，50 mM）和6 μM黄芩苷的组合中来测试其有效性。第三，全胚胎免疫荧光染色和杂交显示，黄芩苷给药可通过上调Pax7和Foxd3的表达来逆转HG抑制的神经嵴细胞（NCC）脱层和迁移，并通过调节相应的黏附分子和转录因子（即E-钙黏蛋白、N-钙黏蛋白、钙黏蛋白6B、锌指蛋白和Msx1）来减轻上皮-间充质转化（EMT）过程的紊乱。最后，通过生物信息学分析和细胞热迁移分析，我们确定AKR1B1基因为潜在靶点。总之，这些发现表明黄芩苷可作为高糖诱导的颅面骨骼畸形的治疗药物。
