title: The role of p21 Waf1/Cip1 in large airway epithelium in smokers with and without COPD.
abstract: 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.
authors: Istituto di Biomedicina e Immunologia Molecolare-Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors: Giuseppina
authors: G
authors: Chiappara
authors: Mark
authors: M
authors: Gjomarkaj
authors: Alessia
authors: A
authors: Virzì
authors: Serafina
authors: S
authors: Sciarrino
authors: Maria
authors: M
authors: Ferraro
authors: Andreina
authors: A
authors: Bruno
authors: Angela Marina
authors: AM
authors: Montalbano
authors: Patrizio
authors: P
authors: Vitulo
authors: Marta Ida
authors: MI
authors: Minervini
authors: Loredana
authors: L
authors: Pipitone
authors: Elisabetta
authors: E
authors: Pace
mesh_terms: D000368:Aged; D001980:Bronchi / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism / Q000502:physiology*; D004848:Epithelium / Q000503:physiopathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D012907:Smoking / Q000503:physiopathology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D053148:Caspase 3
keywords: Apoptosis; CFSE; COPD; CSE; Epithelium; IAPs; Metaplasia; PCNA; Proliferation; S; carboxyfluorescein succinimidyl ester; chronic obstructive pulmonary disease; cigarette smoke extracts; inhibitor of apoptosis proteins; proliferating cell nuclear antigen; smokers