title: N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro.
abstract: Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR's expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801's influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA's direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Zhengchang
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Pediatrics, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Xiangya Medical School, Central South University, Changsha, Hunan 410008, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Huiyi
authors.initials: H
authors.lastname: Huo
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Chuanding
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Shaojie
authors.identifier: 0000-0002-4696-656X
authors.initials: S
authors.lastname: Yue
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D047109:Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D055370:Lung Injury / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016291:Dizocilpine Maleate