Role of notch signaling pathway in Muc5ac secretion induced by atmospheric PM2.5 in rats

Abstract

Background: The secretion of Muc5ac is closely related to the pathogenesis, treatment and prognosis of bronchial asthma. Atmospheric PM_2.5 entered the airway can irritate and corrode the bronchial wall, affecting the expression and secretion of Muc5ac. However, the underlying mechanism is not clear. In this study, we investigated the role of the Notch signaling pathway in mucin section induced by atmospheric PM_2.5 in rats.

Methods: Fifty rats were divided randomly into five groups: the control received physiological saline; the health, health Notch signaling pathway inhibition and asthma, asthma Notch signaling pathway inhibition groups received 7.5 mg/kg PM_2.5. PM_2.5 or saline was instilled into the trachea at 2-day intervals for two doses. IL-1β, TNF-α and Muc5ac levels were detected by ELISA. The mRNA expression levels of Notch signaling pathway genes were detected by real time PCR. The levels of Notch signaling pathway protein were detected by western blot.

Results: The levels of Muc5ac in the lungs and TNF-α in serum of asthmatic rats exposed to PM2.5 was the highest, and when Notch signaling pathway was inhibited, the levels of Muc5ac in the lungs and tracheas and TNF-α in serum of asthmatic rats exposed to PM2.5 was significantly decreased. Hes1 mRNA expression level in trachea was the lowest in the asthma inhibition group; and inhibiting the Notch signaling pathway could decrease the mRNA and protein levels of Hes1 in rats' lung. The mRNA relative levels of Notch3 and Notch4 in rats' trachea, the protein levels of Notch3 in rats' lung, and the mRNA relative levels of Jagged1 and Jaggeed2 in rats' lung were more consist with the changes of Muc5ac, TNF-α and Hes1.

Conclusion: Notch signaling pathway played an important role in Muc5ac secretion induced by atmospheric PM_2.5 of the asthmatic rats' airways. Jagged1 and Jagged2 interacting with Notch3 and Notch4 regulated the expression of Hes1, further regulated TNF-α in the process of PM_2.5 inducing the secretion of Muc5ac.

Keywords: Bronchial asthma; Inflammation; Mucin section; Notch signaling pathway; PM(2.5) toxicity.