Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Role of Notch signaling pathway in bone marrow mesenchymal stem cell therapy for phosgene inhalation-induced lung injury in rats

Yiru Shao^1-3, Jie Shen^1-3 , Fangqing Zhou^1-3, Daikun He^1-3

¹Department of Intensive Care Unit, Center of Emergency & Intensive Care Unit; ²Department of Intensive Care Unit, Medical Research Center of Chemical Injury; ³Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai 201508, China.

For correspondence:- Jie Shen Email: vq1300@163.com Tel:+862584175562

Accepted: 29 November 2018 Published: 26 December 2018

Citation: Shao Y, Shen J, Zhou F, He D. Role of Notch signaling pathway in bone marrow mesenchymal stem cell therapy for phosgene inhalation-induced lung injury in rats. Trop J Pharm Res 2018; 17(12):2399-2404 doi: 10.4314/tjpr.v17i12.13

© 2018 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determining the expression and role of the Notch signaling pathway (NSP) in phosgene inhalation-induced lung injury in rats, and the therapeutic effect of bone marrow mesenchymal stem cell (MSC) on the lung lesions.

Methods: Wistar rats (220 - 280 g) were randomly assigned to air inhalation group, phosgene inhalation group, and mesenchymal stem cell (MSC) intervention group. Each group had 8 rats. Directional flow phosgene inhalation device was used to produce phosgene inhalation-induced lung injury in the rats. Serum inflammatory cytokines (TNF-α, IL-8 and IL-6) were determined using ELISA assay kits. The expressions of proteins related to the NSP (Notch1, Notch2, Hes1, Hes5) were quantified using Western blot.

Results: Phosgene inhalation brought about significant increase in TNF-α, IL-8 and IL-6 levels (p < 0.01), but MSC intervention significantly reduced the expressions of these inflammatory factors to varying degrees (p < 0.05), although their levels were still significantly high, relative to the air inhalation group. Results from western blot showed that the Notch1, Notch2, Hes1 and Hes5 were upregulated in the phosgene inhalation group, when relative to the air inhalation group (p < 0.01). Protein expressions in the MSC intervention group were lower than those in the non-intervention groups (p < 0.05).

Conclusion: Phosgene inhalation activates Notch signaling pathway, while MSC intervention inhibits this signaling pathway. Thus, inhibition of NSP may be implicated in the protective effect of MSC therapy against phosgene-induced lung injury.

Keywords: Phosgene, Lung injury, Notch signalling pathway, Mesenchymal stem cells