The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production

Ming Jie Wang, Zi Qiang Luo, Yinyan Yue, Yan Rui Wang, Shu Wu, Chuan Ding Cao, Zheng Chang Liao, Xiao He Yu, Shao Jie Yue

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Studies have suggested that endogenous glutamate and N-methyl-D-aspartate (NMDA) receptor have an excitotoxity role during acute lung injury. Fibroblasts play a critical role in lung development and chronic lung disease after acute lung injury. This study aims to explore the immediate role of NMDAR activation in human lung fibroblasts. The expression of NMDAR 1 subtype (NR1) and four individual NMDAR 2 (NR2) subtypes (NR 2 A to D) was measured in human fetal lung fibroblasts (HFL-1 and MRC-5). Five NMDARs expression were all detectable in two cell lines. Although the expressions of NMDARs were different between MRC-5 and HFL-1, 1 mM NMDA elicited the same trend in the downregulation of NR2A expression, the upregulation of NR2D, and the increase of cells proliferation and collagen production. Glutamate stimulation after 24-h of NMDA exposure resulted in weaker and more delayed but more prolonged iCa2 + elevation in HFL-1 than no NMDA exposed cells. NMDA increased the level of pERK1/2 cells proliferation and collagen production, whereas nonspecific NMDAR antagonist MK-801, NR2D-preferring receptor antagonist UBP141 and ERK1/2 phosphorylation inhibitor U0126 suppressed it, respectively. In conclusion, we found that NMDAR activation, NR2D in particular, is involved in human fetal lung fibroblast proliferation and collagen production through a potential ERK1/2-mediated mechanism.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalToxicology in Vitro
Volume46
DOIs
StatePublished - Feb 1 2018

Keywords

  • Extracellular signal-regulated kinase
  • Glutamate
  • Lung fibroblast
  • N-methyl-D-aspartate receptor

ASJC Scopus subject areas

  • Toxicology

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