Tropical Journal of Pharmaceutical Research

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

Yiru Shao, Jie Shen, Fangqing Zhou, Daikun He


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
AJOL African Journals Online