阿特拉基列诺利德-I通过直接和间接调节STAT3通路来缓解高血糖引起的心脏发育形
Mengwei Wang1, Tong-Hua Zhang2, Yunjin Li3
1Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, School of Medicine, Jinan University, Guangzhou 510632, China; Department of Cell Biology, College of Life Science and Technology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine; Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University, Guangzhou, 510632, China.
概括
孕期糖尿病增加了先天性心脏缺陷的风险. 阿特拉提利诺利德-I (AT-I) 通过抑制STAT3通路并影响母体肠道微生物群来保护,减少胎儿心脏异常.
科学领域:
- 生殖生物学和发育毒理学.
- 药理学和传统医学.
- 心血管研究的心血管研究.
背景情况:
- 孕期糖尿病 (GDM) 与婴儿先天性心脏缺陷 (CHD) 的风险增加有关.
- 目前用于预防或治疗GDM诱导的心脏病的治疗方法有限.
- 阿特拉提利诺化物-I (AT-I),源自传统的中国草药Atractylodes Macrocephala Koidz,正在研究其在怀孕期间的潜在益处.
研究的目的:
- 在胚胎模型中研究阿特拉提利诺利德-I (AT-I) 对高葡萄糖诱导的先天性心脏缺陷 (CHD) 的保护作用.
- 阐明AT-I减轻心脏细胞中氧化应激和亡的潜在分子机制.
- 在孕期糖尿病的哺乳动物模型中评估AT-I在预防胎儿心脏发育异常方面的有效性.
主要方法:
- 系统性审查确定了GDM,心血管形,氧化应激和亡之间的联系.
- 在H9c2细胞和胚胎上进行了阿特拉基烯化物化合物的细胞毒性评估.
- 使用免疫光学,西斑,PCR和流细胞计,包括STAT3通路相互作用的分子对接,探索了作用机制.
- 一个小鼠模型的怀孕与链毒素诱导的糖尿病 (PGDM) 已建立在体内评估.
- 进行了微生物群和非向代谢学分析,以了解AT-I对母亲肠道健康和胎儿发育的影响.
主要成果:
- 在胚胎模型中,AT-I证明了保护作用,抵消高葡萄糖诱导的活性氧物种 (ROS) 和细胞死亡.
- 有证据表明,AT-I与STAT3直接相互作用,抑制其酸化.
- 在PGDM小鼠模型中,AT-I部分改善了血糖控制,并减少了高血糖引起的胎儿心脏异常.
- 假设AT-I的保护作用涉及对母体肠道微生物群组成和下游信号通路 (EGFR/STAT3) 的调节.
结论:
- AT-I有效地减少与妊娠糖尿病相关的早期心脏发育异常.
- AT-I抑制了ROS激活的STAT3通路,从而减轻胎儿心脏异常.
- 通过影响母体肠道微生物群和抑制EGFR/STAT3通路,AT-I还间接支持胎儿正常心脏发育.
相关概念视频
01:20The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K
01:16TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
03:14Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K