Altered expression of p21, activated caspase-3, and PCNA in bronchiolar epithelium of smokers with and without chronic obstructive pulmonary disease
Altered expression of p21, activated caspase-3, and PCNA in bronchiolar epithelium of smokers with and without chronic obstructive pulmonary disease
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DOI：
10.3109/01902148.2014.928836
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发表时间：
2014-09-01
影响因子：
1.7
通讯作者：
Pace, Elisabetta
中科院分区：
文献类型：
--
作者：
Chiappara, Giuseppina;Gjomarkaj, Mark;Pace, Elisabetta
背景：细胞周期蛋白依赖性激酶抑制剂 p21CIP1/WAF1 参与细胞应激源（如香烟烟雾）导致的细胞周期生长停滞。 p21 在细胞凋亡中的作用存在争议，因为它在不同的细胞中发挥促凋亡或抗凋亡作用。在本研究中，我们研究了患有和不患有 COPD 的吸烟者小气道上皮中 p21 表达的改变是否与增殖和凋亡之间的不平衡有关。目的和方法：在患有和不患有 COPD 的吸烟者以及不吸烟的非 COPD 受试者的小气道（细支气管）上皮中评估参与细胞凋亡调节的特定分子的表达，例如激活的 caspase-3 和细胞质 p21、细胞静止 (G(0)) 或增殖标记物（例如 Ki67 和 PCNA）以及细胞周期标记物（例如核 p21）。结果：在患有和不患有 COPD 的吸烟者中，我们发现细胞质核 p21 和激活的 caspase-3 表达增加。相比之下，我们在所有研究组中验证了吸烟者和患有 COPD 的吸烟者中增殖标记物 Ki67 的类似低表达和 PCNA 表达的减少。结论：在小气道上皮中，与激活的 caspase-3 表达增加相关的细胞质 p21 可能发挥促凋亡作用。此外，p21 的改变可能与吸烟者和患有 COPD 的吸烟者的组织修复抑制有关，PCNA 等增殖标志物的低表达证实了这一点。所有这些事件可能在导致细支气管组织破坏的永久性细胞损伤中发挥作用。
Background: The cyclin-dependent kinase inhibitor p21CIP1/WAF1 is involved in cell-cycle growth arrest due to cell stressors, such as cigarette smoke. The role of p21 in cell apoptosis is controversial as it exerts pro- or antiapoptotic effects in different cells. In the present study, we investigated whether, in the epithelium of small airways of smokers with and without COPD, altered p21 expression is associated with an imbalance between proliferation and apoptosis. Objectives and Methods: The expression of specific molecules involved in the regulation of apoptosis, such as activated caspase-3 and cytoplasmic p21, cell quiescence (G(0)) or proliferation markers such as Ki67 and PCNA, and cell-cycle markers such as the nuclear p21, was assessed in the small airway (bronchiolar) epithelium of smokers with and without COPD and in nonsmoker non-COPD subjects. Results: In smokers with and without COPD, we found an increase of cytoplasmic nuclear p21 and activated caspase-3 expression. By contrast, we verified in all the studied groups a similar low expression of the proliferation marker Ki67 and a reduced expression of PCNA in smokers and smokers with COPD. Conclusions: In the small airway epithelium, cytoplasmic p21 correlating with increased activated caspase-3 expression might play a proapoptotic role. Furthermore, p21 alteration may be associated with the inhibition of tissue repair in smokers and smokers with COPD as confirmed by the low expression of proliferation markers such as PCNA. All these events may play a role in the permanent cellular damage leading to the destruction of bronchiolar tissue.