CD147 increases mucus secretion induced by cigarette smoke in COPD

Abstract

BackgroundCD147 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.MethodsWe 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.ResultsCompared 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (10.1186/s12890-019-0791-0) contains supplementary material, which is available to authorized users.

Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses

“…Normal epithelial and fetal tissues have low expression of CD147, when measured by immunohistochemical analysis [ 54 ]. However, CD147 is significantly upregulated in aggressive and chronic disease states, such as in cancers [ 55 , 56 ], atherosclerosis [ 57 ], diabetes [ 58 ], ischemic stroke [ 59 ], and chronic lung obstruction diseases [ 60 ]. Intriguingly, recent studies show that CD147 plays a functional role in facilitating SARS-CoV-1 and SARS-CoV-2 entry [ 22 , 61 ], and antibody against CD147 blocks the infection of SARS-CoV-2 [ 22 ].…”

Severe Acute Respiratory Syndrome–Associated Coronavirus 2 Infection and Organ Dysfunction in the ICU: Opportunities for Translational Research

“…SARS-CoV-2 enters cells (by exploiting Spike protein sites) via ACE2, dipeptidyl peptidase 4 (DPP4), CD147 (a highly glycosylated cell surface protein with wide tissue expression), or the cathepsin pathway to cleave and facilitate viral entry ( 72 – 75 ). Blocking DPP4 attenuates ALI in a murine model, and DPP4 has been studied in airway remodeling and fibrosis, whereas CD147 has been implicated in mucus hypersecretion ( 76 – 78 ). Thus, identifying all receptors/proteases involved in SARS-CoV-2 respiratory infection will enhance our mechanistic insight into disease pathogenesis.…”

Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147)

“…Targeting CD147 have been shown to reduce inflammation and severity of the disease by affecting these ligands in asthmatic pulmonary inflammation, multiple sclerosis and myocardial ischemia/reperfusion injury [ 20 – 22 ]. Previous studies have noted that the expression of CD147 increases matrix metalloproteinase (MMP) activity, which is induced by MAPKs-bound Angiotensin II [ 23 – 25 ]. Additionally, CD147 plays a role in inflammation that develops through pro-inflammatory cytokines, including interleukin-6 (IL-6), interferon-gamma (IFN-γ), tumor-necrosis factor-α (TNF-α), and monocyte chemo-attractant protein-1 (MCP-1) [ 26 ].…”