The excitotoxity of NMDA receptor NR2D subtype mediates human fetal lung fibroblasts proliferation and collagen production
Autor: | Ming Jie Wang, Chuan Ding Cao, Shu Wu, Zi Qiang Luo, Zheng Chang Liao, Yinyan Yue, Shao Jie Yue, Yan Rui Wang, Xiao He Yu |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Cell Survival medicine.drug_class Glutamic Acid Lung injury Biology Toxicology Receptors N-Methyl-D-Aspartate Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Humans Extracellular Signal-Regulated MAP Kinases Receptor Fibroblast Lung Cell Proliferation Glutamate receptor General Medicine Fibroblasts Receptor antagonist 030104 developmental biology Endocrinology medicine.anatomical_structure Gene Expression Regulation nervous system Cell culture Immunology NMDA receptor Calcium Collagen Dizocilpine Maleate 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Toxicology in Vitro. 46:47-57 |
ISSN: | 0887-2333 |
Popis: | 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, 1mM 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. |
Databáze: | OpenAIRE |
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