CD147 increases mucus secretion induced by cigarette smoke in COPD

Qiao Yu  ¹ , Danhui Yang  ² , Xi Chen  ³ , Qiong Chen  ⁴

• ¹ Department of Gerontology and Respirology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
• ² Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
• ³ Department of Respiratory Medicine, Xiangya of Central South University, Changsha, 410008, Hunan, China.
• ⁴ Department of Gerontology and Respirology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China. qiongch@163.com.

Abstract

Background: CD147 is expressed in many tissues and is involved in many inflammatory diseases. Emerging evidence suggests that the overproduction of mucus is a malignant factor in chronic obstructive pulmonary disease (COPD), which results in severe airway obstruction and repeated airway infections. However, it is still unclear whether CD147 is involved in mucus production in COPD.

Methods: We determined the expression levels of CD147 and MUC5AC by immunohistochemistry in 42 human lung specimens from three groups (non-smokers without COPD, smokers without COPD and smokers with COPD). For the in vitro experiment, human bronchial epithelial (HBE) cells were treated with cigarette smoke (CS) extract to establish a mucus secretion model; then, CD147 and MUC5AC production were detected by RT-PCR, Western blotting and ELISA. To determine how CD147 is involved in MUC5AC secretion, HBE cells were transfected with small interfering RNA to silence CD147 and pretreated with inhibitors of MMP9 and p38 MAPK, which are common signaling molecules involved in MUC5AC secretion; then, MUC5AC expression was evaluated.

Results: Compared with the expression levels in the non-smokers and smokers without COPD, CD147 and MUC5AC expression levels were higher in the smokers with COPD. In the in vitro experiment, CD147 and MUC5AC expression levels were significantly increased after CS extract incubation compared with those after no treatment. Silencing CD147 by siRNA decreased the CS extract-induced MUC5AC secretion and MMP9 and phosphorylated p38 MAPK production. In addition, inhibiting MMP9 or p38 MAPK decreased the CS extract-induced MUC5AC secretion.

Conclusions: In lung specimens, CD147 and MUC5AC expression levels were increased in COPD patients. Increased CD147 levels induced by CS extract could stimulate MUC5AC secretion through the MMP9 and p38 MAPK signaling pathway in HBE cells. Therefore, the regulation of CD147 could be a promising target for mucus hypersecretion in COPD.

Keywords: CD147; COPD; Cigarette smoke extract; MMP9; MUC5AC; Mucus; p38 MAPK.