Altered expression of p21, activated caspase-3, and PCNA in bronchiolar epithelium of smokers with and without chronic obstructive pulmonary disease

Giuseppina Chiappara, Mark Gjomarkaj, Serafina Sciarrino, Patrizio Vitulo, Loredana Pipitone, Elisabetta Pace

Research output: Contribution to journalArticlepeer-review

Abstract

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 (G0) 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.

Original languageEnglish
Pages (from-to)343-353
Number of pages11
JournalExperimental Lung Research
Volume40
Issue number7
DOIs
Publication statusPublished - 2014

Keywords

  • Cigarette smoke
  • Distal airways
  • Epithelium
  • Injury
  • Lung

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Medicine(all)

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