Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia

Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pr...

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Main Authors: Tsung-Lin Cheng, Chung-Hwan Chen, Meng-Hsing Wu, Chao-Han Lai, Ko-Hung Lee, Sheng-Hsiang Lin, Ai-Li Shiau, Chao-Liang Wu, Lin Kang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.757643/full
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author Tsung-Lin Cheng
Tsung-Lin Cheng
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Meng-Hsing Wu
Chao-Han Lai
Chao-Han Lai
Ko-Hung Lee
Sheng-Hsiang Lin
Ai-Li Shiau
Chao-Liang Wu
Lin Kang
author_facet Tsung-Lin Cheng
Tsung-Lin Cheng
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Meng-Hsing Wu
Chao-Han Lai
Chao-Han Lai
Ko-Hung Lee
Sheng-Hsiang Lin
Ai-Li Shiau
Chao-Liang Wu
Lin Kang
author_sort Tsung-Lin Cheng
collection DOAJ
description Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7–14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8–20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.
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spelling doaj.art-44c8c8a6bd8047b08c4723e96db25f0e2022-12-21T23:11:40ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-12-01910.3389/fcell.2021.757643757643Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of PreeclampsiaTsung-Lin Cheng0Tsung-Lin Cheng1Chung-Hwan Chen2Chung-Hwan Chen3Chung-Hwan Chen4Chung-Hwan Chen5Meng-Hsing Wu6Chao-Han Lai7Chao-Han Lai8Ko-Hung Lee9Sheng-Hsiang Lin10Ai-Li Shiau11Chao-Liang Wu12Lin Kang13Department of Physiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanRegenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanOrthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Adult Reconstruction Surgery, Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanAn-an Women and Children Clinic, Tainan, Taiwan0College of Medicine, Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan1Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanFibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7–14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8–20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.https://www.frontiersin.org/articles/10.3389/fcell.2021.757643/fullfibrinogen-like 1preeclampsiaplacentaembryo (animal)proinflammatory cytokines
spellingShingle Tsung-Lin Cheng
Tsung-Lin Cheng
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Chung-Hwan Chen
Meng-Hsing Wu
Chao-Han Lai
Chao-Han Lai
Ko-Hung Lee
Sheng-Hsiang Lin
Ai-Li Shiau
Chao-Liang Wu
Lin Kang
Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
Frontiers in Cell and Developmental Biology
fibrinogen-like 1
preeclampsia
placenta
embryo (animal)
proinflammatory cytokines
title Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
title_full Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
title_fullStr Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
title_full_unstemmed Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
title_short Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia
title_sort upregulation of fibrinogen like 1 expression contributes to reducing the progression of preeclampsia
topic fibrinogen-like 1
preeclampsia
placenta
embryo (animal)
proinflammatory cytokines
url https://www.frontiersin.org/articles/10.3389/fcell.2021.757643/full
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