FGF4, A New Potential Regulator in Gestational Diabetes Mellitus
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.Me...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.827617/full |
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| author | Miaojuan Fan Miaojuan Fan Miaojuan Fan Tongtong Pan Wei Jin Wei Jin Jian Sun Shujun Zhang Yali Du Xinwei Chen Qiong Chen Wenxin Xu Siew Woh Choo Guanghui Zhu Yongping Chen Jie Zhou Jie Zhou |
| author_facet | Miaojuan Fan Miaojuan Fan Miaojuan Fan Tongtong Pan Wei Jin Wei Jin Jian Sun Shujun Zhang Yali Du Xinwei Chen Qiong Chen Wenxin Xu Siew Woh Choo Guanghui Zhu Yongping Chen Jie Zhou Jie Zhou |
| author_sort | Miaojuan Fan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T01:09:48Z |
| format | Article |
| id | doaj.art-f7970e3545324fd8b7bc6f4eb82933eb |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-24T01:09:48Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f7970e3545324fd8b7bc6f4eb82933eb2022-12-21T17:23:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.827617827617FGF4, A New Potential Regulator in Gestational Diabetes MellitusMiaojuan Fan0Miaojuan Fan1Miaojuan Fan2Tongtong Pan3Wei Jin4Wei Jin5Jian Sun6Shujun Zhang7Yali Du8Xinwei Chen9Qiong Chen10Wenxin Xu11Siew Woh Choo12Guanghui Zhu13Yongping Chen14Jie Zhou15Jie Zhou16Department of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaBaoji Maternal and Child Health Hospital, Baoji, ChinaDepartment of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Fourth Affiliated Hospital, Zhejiang University School of Medicine, Jinhua, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaCollege of Science and Technology, Wenzhou-Kean University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Infectious Diseases & Zhejiang Provincial Key laboratory of Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.827617/fullgestational diabetes mellitusFGF4embryopathyneural tube defectsplacenta |
| spellingShingle | Miaojuan Fan Miaojuan Fan Miaojuan Fan Tongtong Pan Wei Jin Wei Jin Jian Sun Shujun Zhang Yali Du Xinwei Chen Qiong Chen Wenxin Xu Siew Woh Choo Guanghui Zhu Yongping Chen Jie Zhou Jie Zhou FGF4, A New Potential Regulator in Gestational Diabetes Mellitus Frontiers in Pharmacology gestational diabetes mellitus FGF4 embryopathy neural tube defects placenta |
| title | FGF4, A New Potential Regulator in Gestational Diabetes Mellitus |
| title_full | FGF4, A New Potential Regulator in Gestational Diabetes Mellitus |
| title_fullStr | FGF4, A New Potential Regulator in Gestational Diabetes Mellitus |
| title_full_unstemmed | FGF4, A New Potential Regulator in Gestational Diabetes Mellitus |
| title_short | FGF4, A New Potential Regulator in Gestational Diabetes Mellitus |
| title_sort | fgf4 a new potential regulator in gestational diabetes mellitus |
| topic | gestational diabetes mellitus FGF4 embryopathy neural tube defects placenta |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.827617/full |
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