title: N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats.
abstract: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions.
  
  
  
  In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8). The role of NMDAR activation in hyperoxia-induced lung fibroblast proliferation and differentiation was examined in vitro using primary cells derived from the lungs of 8-day-old Sprague-Dawley rats exposed to hyperoxic conditions.
  
  
  
  Hyperoxia for 3 days induced acute lung injury in newborn rats. The acute injury almost completely disappeared 4 days after cessation of hyperoxia exposure. However, pulmonary fibrosis, impaired alveolarization, and decreased pulmonary compliance were observed on postnatal days 15 and 22. MK-801 treatment during the recovery period was found to alleviate the chronic damage induced by hyperoxia. Four NMDAR 2 s were found to be upregulated in the lung fibroblasts of newborn rats exposed to hyperoxia. In addition, the proliferation and upregulation of alpha-smooth muscle actin and (pro) collagen I in lung fibroblasts were detected in hyperoxia-exposed rats. MK-801 inhibited these changes.
  
  
  
  NMDAR activation mediated lung fibroblast proliferation and differentiation and played a role in the development of hyperoxia-induced chronic lung damage in newborn rats.
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.|Department of Neonatology, Heze Municipal Hospital, Heze, 274000, China.
authors: YanRui
authors: Y
authors: Wang
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.
authors: ShaoJie
authors: S
authors: Yue
authors: Department of Physiology, Xiangya Medical College, Central South University, Changsha, 410008, China.
authors: ZiQiang
authors: Z
authors: Luo
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.
authors: ChuanDing
authors: C
authors: Cao
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.
authors: XiaoHe
authors: X
authors: Yu
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.
authors: ZhengChang
authors: Z
authors: Liao
authors: Department of Neonatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China. xywangmj@163.com.
authors: MingJie
authors: M
authors: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018496:Hyperoxia / Q000150:complications*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011347:Procollagen / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000199:Actins; D024042:Collagen Type I; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D011347:Procollagen; D016194:Receptors, N-Methyl-D-Aspartate; C498862:Acta2 protein, rat
keywords: Chronic lung disease; Hyperoxia; Lung fibroblast; N-methyl-D-aspartate receptor; Newborn