Front. Pharmacol , 2022, Vol13,1663-9812,Text Full
Tang Deng , Qifeng Huang , Kaiwen Lin , Jin Qian , Qi Li , Lihua Li, Shuangqin Xu,
Hongfang Yun , Hangfei Wang , Xinxin Wu , Heng Liu *, Guiyun Jin1 * and Xiaoran Liu*【刘笑然】
doi: 10.3389/fphar.2022.794952
Abstract：
Inflammation-induced proliferation of airway smooth muscle cells (ASMCs) and subsequent airway remodeling is a hallmark of chronic obstructive lung disease(COPD). The role of midkine (MK) in COPD is unclear. In this work, we explored the
role of MK-Notch2 signaling in COPD by inhibiting the expression of MK using lentivirus shRNA in ASMCs in vitro and instillation of AAV9-MK in the airway of a COPD rat model in vivo. The results demonstrated that LPS decreased ASMC migration and proliferation,increased apoptosis and induced the expression of MK and Notch2 signaling molecules.Inhibition of MK exacerbated the changes in migration and proliferation but decreased the expression of MK and Notch2 signaling molecules. Rats treated with smoke fumigation and LPS showed features of COPD. The small airways of COPD rats were remodeled and lung function was signifificantly reduced. The expressions of TGF-β, ICAM-1, HA, MMP-9,PC-III, and LN in BALF and the expression of MK and Notch2 signaling molecules were signifificantly increased in the COPD rats compared with controls. Inhibition of MK reversed
these changes. In conclusion, the MK-Notch2 pathway plays a key role in airway remodeling induced by ASMC proliferation. Targeting the MK-Notch2 pathway may be a new strategy for improving airway remodeling and preventing progressive decline of
pulmonary function in COPD.
