4.5 Article

Human placenta mesenchymal stem cells suppress airway inflammation in asthmatic rats by modulating Notch signaling

Journal

MOLECULAR MEDICINE REPORTS
Volume 17, Issue 4, Pages 5336-5343

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2018.8462

Keywords

asthma; hPMSCs; Notch; lymph; rats

Funding

  1. Shandong Province Natural Science Foundation of China [ZR2011HM081]
  2. Yantai Science and Technology Development Funds [2008142-11]
  3. Taishan Scholar Foundation

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Neurogenic locus notch homolog protein (Notch) signaling mediates intracellular communication and may regulate cell fate decisions, including cell proliferation, differentiation, and apoptosis. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and the potential for use in stem cell replacement treatments. The aim of the present study was to evaluate the therapeutic effects of human placenta-deviated MSCs (hPMSCs) in asthma and to investigate the mechanisms of Notch signaling mediated by transplanted MSCs. A Sprague-Dawley rat ovalbumin (OVA)-sensitized acute asthma model was established and challenged. MSCs derived from human placenta (hPMSCs) were transplanted into the asthmatic rats. Transplantation resulted in reduced Notch-1, Notch-2 and jagged-1, and increased Notch-3, Notch-4 and delta-like ligand (delta)-4 expression in lung, blood, and lymph samples. Notch-1, Notch-2, and jagged-1 expression in OVA-treated rats was significantly decreased compared with controls and hPMSC-treated rats; however, Notch-3, Notch-4 and delta-4 expression was significantly increased. Serum interferon- significantly increased after hPMSCs transplantation, whereas interleukin-4 and immunoglobulin E decreased. In OVA-treated rats, Notch-1, Notch-2 and jagged-1 levels were increased in the lymph compared with the blood, although Notch-4 and delta-4 levels were decreased. Peribronchial infiltration of cells and goblet cell hyperplasia were markedly decreased in the OVA + hPMSCs group compared with those in the OVA-treated and control groups. Alterations in Notch signaling pathway expression were accompanied by decreased inflammatory cell infiltration, goblet cell hyperplasia and mucus production in lung tissues. The results of the present study are consistent with hPMSC suppression of asthma symptoms and inflammation by regulating the Notch signaling pathway in the rat asthma model.

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