Brain-Derived Neurotrophic Factor Inhibits the Wound-Healing and Cell Proliferative Ability of Human Airway Epithelial Cells in Asthmatic Children

脑源性神经营养因子抑制哮喘儿童人气道上皮细胞的伤口愈合和细胞增殖能力

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作者:Shuguang Jing, Xinghua Li, Wei Liu, Xia Li

Abstract

BACKGROUND Asthma is a chronic disease with high morbidity rates. Brain-derived neurotrophic factor (BDNF) has been proven to induce airway hyper-responsiveness, but the function of BDNF in the wound-healing process of asthmatic human airway epithelial cells (HAECs) remains unclear. This study investigated the effects of BDNF in asthmatic children with injured HAECs. MATERIAL AND METHODS HAECs were obtained from healthy children and asthmatic children through bronchoscopy, and then cultured in air-liquid (ALI) interface with or without BDNF. A mechanical injury model was established for the wound-healing assay. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to measure BDNF mRNA expressions, while western blot assay was used for the measurement of BDNF and CCND1 protein expressions. Cell proliferation of impaired HAECs was assayed in a ³H-thymidine incorporation experiment. RESULTS The mRNA and protein levels of BDNF were overexpressed, and the wound-healing ability of HAECs decreased in asthma samples. Also, the cell proliferation of HAECs was suppressed in the asthmatic injury model and the injury-induced increase of CCND1 protein expressions was inhibited in asthma. Although mRNA and protein expressions of BDNF remained unchanging in healthy HAECs, there was an increase in impaired asthmatic HAECs. Upregulating BDNF led to a decrease in wound-healing ability of HAECs in both healthy children and children with asthma. Simultaneously, overexpressed BDNF reduced the CCND1 protein expressions in healthy HAECs, but had little impact on asthmatic HAECs. CONCLUSIONS Brain-derived neurotrophic factor (BDNF) inhibited wound-healing and cell proliferative ability of human airway epithelial cells (HAECs) in asthmatic children.

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