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Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.
Zhu, Haibin; Luo, Huan; Wu, Xiaowei; Bao, Hangyang; Shu, Yingying; Ji, Xing; Fan, Xueying; Pan, Yibin; Tang, Chao; Wu, Ximei; Ruan, Hongfeng.
Afiliación
  • Zhu H; Department of Gynaecology, the First Affiliated Hospital, Zhejiang Univerisity School of Medicine, Hangzhou, 310009, China. zhuhb@zju.edu.cn.
  • Luo H; Department of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
  • Wu X; Department of Gynaecology, the First Affiliated Hospital, Zhejiang Univerisity School of Medicine, Hangzhou, 310009, China.
  • Bao H; Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, 310053, Zhejiang, China.
  • Shu Y; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China.
  • Ji X; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China.
  • Fan X; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China.
  • Pan Y; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China.
  • Tang C; Department of Obstetrics and Gynaecology, the Affiliated Sir Run Run Shaw Hospital, Zhejiang Univerisity School of Medicine, Hangzhou, 310016, China.
  • Wu X; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China.
  • Ruan H; Department of Pharmacology, Zhejiang Univerisity School of Medicine, Hangzhou, 310058, China. xiwu@zju.edu.cn.
Cell Mol Life Sci ; 81(1): 303, 2024 Jul 15.
Article en En | MEDLINE | ID: mdl-39008099
ABSTRACT
Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placentación / Ácido Ascórbico / Trofoblastos / Diferenciación Celular / Proteínas Quinasas JNK Activadas por Mitógenos / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Placentación / Ácido Ascórbico / Trofoblastos / Diferenciación Celular / Proteínas Quinasas JNK Activadas por Mitógenos / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza