CD147 增加 COPD 患者香烟烟雾诱导的黏液分泌。
CD147 increases mucus secretion induced by cigarette smoke in COPD.
机构信息
Department of Gerontology and Respirology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
出版信息
BMC Pulm Med. 2019 Feb 6;19(1):29. doi: 10.1186/s12890-019-0791-0.
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.
背景
CD147 在许多组织中表达，并参与许多炎症性疾病。新出现的证据表明，黏液的过度产生是慢性阻塞性肺疾病（COPD）的一个恶性因素，导致严重的气道阻塞和反复的气道感染。然而，CD147 是否参与 COPD 中的黏液产生仍不清楚。
方法
我们通过免疫组织化学法检测了 42 个人肺标本中 CD147 和 MUC5AC 的表达水平，这些标本来自三组人群（非 COPD 的不吸烟者、无 COPD 的吸烟者和有 COPD 的吸烟者）。在体外实验中，用人支气管上皮（HBE）细胞用香烟烟雾（CS）提取物处理来建立黏液分泌模型；然后通过 RT-PCR、Western blot 和 ELISA 检测 CD147 和 MUC5AC 的产生。为了确定 CD147 如何参与 MUC5AC 的分泌，我们用小干扰 RNA 转染 HBE 细胞沉默 CD147，并预先用 MMP9 和 p38 MAPK 的抑制剂处理，这两种抑制剂是参与 MUC5AC 分泌的常见信号分子；然后评估 MUC5AC 的表达。
结果
与非吸烟者和无 COPD 的吸烟者相比，COPD 吸烟者的 CD147 和 MUC5AC 表达水平更高。在体外实验中，与无处理相比，CS 提取物孵育后 CD147 和 MUC5AC 的表达水平显著增加。用 siRNA 沉默 CD147 可降低 CS 提取物诱导的 MUC5AC 分泌以及 MMP9 和磷酸化 p38 MAPK 的产生。此外，抑制 MMP9 或 p38 MAPK 可降低 CS 提取物诱导的 MUC5AC 分泌。
结论
在肺标本中，COPD 患者的 CD147 和 MUC5AC 表达水平增加。CS 提取物诱导的 CD147 水平升高可通过 HBE 细胞中的 MMP9 和 p38 MAPK 信号通路刺激 MUC5AC 分泌。因此，CD147 的调节可能是 COPD 中黏液过度分泌的一个有希望的靶点。
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