Chiappara Giuseppina, Gjomarkaj Mark, Virzì Alessia, Sciarrino Serafina, Ferraro Maria, Bruno Andreina, Montalbano Angela Marina, Vitulo Patrizio, Minervini Marta Ida, Pipitone Loredana, Pace Elisabetta
Istituto di Biomedicina e Immunologia Molecolare-Consiglio Nazionale delle Ricerche, Palermo, Italy.
Biochim Biophys Acta. 2013 Oct;1832(10):1473-81. doi: 10.1016/j.bbadis.2013.04.022. Epub 2013 Apr 29.
Airway epithelium alterations, including squamous cell metaplasia, characterize smokers with and without chronic obstructive pulmonary disease (COPD). The p21 regulates cell apoptosis and differentiation and its role in COPD is largely unknown. Molecules regulating apoptosis (cytoplasmic p21, caspase-3), cell cycle (nuclear p21), proliferation (Ki67/PCNA), and metaplasia (survivin) in central airways from smokers (S), smokers-COPD (s-COPD) and non-smokers (Controls) were studied. The role of cigarette smoke extracts (CSE) in p21, survivin, apoptosis (caspase-3 and annexin-V binding) and proliferation was assessed in a bronchial epithelial cell line (16HBE). Immunohistochemistry, image analysis in surgical samples and flow-cytometry and carboxyfluorescein succinimidyl ester proliferative assay in 16HBE with/without CSE were applied. Cytoplasmic and nuclear p21, survivin, and Ki67 expression significantly increased in large airway epithelium in S and in s-COPD in comparison to Controls. Caspase-3 was similar in all the studied groups. p21 correlated with epithelial metaplasia, PCNA, and Ki67 expression. CSE increased cytoplasmic p21 and survivin expression but not apoptosis and inhibited the cell proliferation in 16HBE. In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark.
气道上皮改变，包括鳞状细胞化生，是患有和未患有慢性阻塞性肺疾病（COPD）的吸烟者的特征。p21调节细胞凋亡和分化，其在COPD中的作用很大程度上未知。研究了吸烟者（S）、吸烟合并COPD者（s-COPD）和非吸烟者（对照组）中央气道中调节细胞凋亡（细胞质p21、半胱天冬酶-3）、细胞周期（细胞核p21）、增殖（Ki67/增殖细胞核抗原）和化生（生存素）的分子。在支气管上皮细胞系（16HBE）中评估香烟烟雾提取物（CSE）对p21、生存素、细胞凋亡（半胱天冬酶-3和膜联蛋白-V结合）和增殖的作用。应用免疫组织化学、手术样本图像分析以及对有或无CSE的16HBE进行流式细胞术和羧基荧光素琥珀酰亚胺酯增殖试验。与对照组相比，S组和s-COPD组大气道上皮中的细胞质和细胞核p21、生存素以及Ki67表达显著增加。所有研究组中的半胱天冬酶-3相似。p21与上皮化生、增殖细胞核抗原和Ki67表达相关。CSE增加了16HBE中的细胞质p21和生存素表达，但未增加细胞凋亡，并抑制了细胞增殖。在患有和未患有COPD的吸烟者的大气道上皮中，细胞质p21抑制细胞凋亡，促进细胞增殖，并与鳞状细胞化生相关，因此代表了一种潜在的致癌前标志。
