FGF4, A New Potential Regulator in Gestational Diabetes Mellitus.
FGF4, A New Potential Regulator in Gestational Diabetes Mellitus.
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FGF4，妊娠糖尿病的新潜在调节剂
DOI：
10.3389/fphar.2022.827617
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Fan M;Pan T;Jin W;Sun J;Zhang S;Du Y;Chen X;Chen Q;Xu W;Choo SW;Zhu G;Chen Y;Zhou J
背景：妊娠期糖尿病（GDM）与不良孕产妇和新生儿结局相关，但其潜在机制仍不清楚。本研究的目的是寻找FGFs针对GDM发病机制的有效调节剂，并探讨FGFs在GDM中的作用。方法：我们对 GDM 患者的胎盘 FGF 进行了系统筛查，并进一步在两种不同的 GDM 小鼠模型中进行了研究，以研究其表达变化。选择、改造、纯化显着变化的FGF4并用于治疗GDM小鼠，以检验其是否能够调节糖尿病小鼠的不良代谢表型并保护其胎儿。结果：我们发现 GDM 患者中 FGF4 表达升高，且其水平与血糖呈正相关，表明 FGF4 与 GDM 的发生具有生理相关性。重组 FGF4 (rFGF4) 治疗可以有效地使高脂饮食诱导的 GDM 小鼠的不良代谢表型正常化，但不能使 STZ 诱导的 GDM 小鼠的不良代谢表型正常化。然而，rFGF4 在减少两种 GDM 模型中胚胎神经管缺陷 (NTD) 方面均非常有效。从机制上讲，rFGF4 治疗可抑制两种 GDM 模型的促炎信号级联和神经上皮细胞凋亡，且与葡萄糖调节无关。结论/解释：我们的研究为胎盘 FGF4 的重要作用提供了新的见解，并表明它可能作为 GDM 有前途的诊断因素和治疗靶点。
Background: Gestational diabetes mellitus (GDM) is associated with adverse maternal and neonatal outcomes, however the underlying mechanisms remain elusive. The aim of this study was to find efficient regulator of FGFs in response to the pathogenesis of GDM and explore the role of the FGFs in GDM. Methods: We performed a systematic screening of placental FGFs in GDM patients and further in two different GDM mouse models to investigate their expression changes. Significant changed FGF4 was selected, engineered, purified, and used to treat GDM mice in order to examine whether it can regulate the adverse metabolic phenotypes of the diabetic mice and protect their fetus. Results: We found FGF4 expression was elevated in GDM patients and its level was positively correlated to blood glucose, indicating a physiological relevance of FGF4 with respect to the development of GDM. Recombinant FGF4 (rFGF4) treatment could effectively normalize the adverse metabolic phenotypes in high fat diet induced GDM mice but not in STZ induced GDM mice. However, rFGF4 was highly effective in reduce of neural tube defects (NTDs) of embryos in both the two GDM models. Mechanistically, rFGF4 treatment inhibits pro-inflammatory signaling cascades and neuroepithelial cell apoptosis of both GDM models, which was independent of glucose regulation. Conclusions/interpretation: Our study provides novel insight into the important roles of placental FGF4 and suggests that it may serve as a promising diagnostic factor and therapeutic target for GDM.
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DOI：
10.1002/hep.31568
发表时间：
2021-06
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Lin Q;Huang Z;Cai G;Fan X;Yan X;Liu Z;Zhao Z;Li J;Li J;Shi H;Kong M;Zheng MH;Conklin DJ;Epstein PN;Wintergerst KA;Mohammadi M;Cai L;Li X;Li Y;Tan Y
通讯作者：
Tan Y
影响因子：
5.6
作者：
Kumagai A;Itakura A;Koya D;Kanasaki K
通讯作者：
Kanasaki K
影响因子：
29
作者：
Coate KC;Hernandez G;Thorne CA;Sun S;Le TDV;Vale K;Kliewer SA;Mangelsdorf DJ
通讯作者：
Mangelsdorf DJ
DOI：
10.1038/nrm3528
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
通过调节 FGF1-FGF 受体二聚体稳定性解偶联 FGF1 的有丝分裂和代谢功能
影响因子：
8.8
作者：
Huang Z;Tan Y;Gu J;Liu Y;Song L;Niu J;Zhao L;Srinivasan L;Lin Q;Deng J;Li Y;Conklin DJ;Neubert TA;Cai L;Li X;Mohammadi M
通讯作者：
Mohammadi M