ArticleRespiratory research2007
Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis.
Article in Respiratory research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Trial
- High BMP7 Expression May Worsen Airway Disease in COPD by Altering Epithelial Cell Behavior.International journal of chronic obstructive pulmonary disease · 2025Article
- Unravelling the Role ofAntioxidants (Basel, Switzerland) · 2024Article
- Role of the redox state of the Pirin-bound cofactor on interaction with the master regulators of inflammation and other pathways.PloS one · 2023Article
- Pirin, an Nrf2-Regulated Protein, Is Overexpressed in Human Colorectal Tumors.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Disparities in COVID-19 severities and casualties across ethnic groups around the globe and patterns of ACE2 and PIR variants.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021Article
- Review
- High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis.Cancers · 2020Review
- Article
- Oxidative stress in female cancers.Oncotarget · 2018Review
- Upregulation of PIR gene expression induced by human papillomavirus E6 and E7 in epithelial oral and cervical cells.Open biology · 2017Article
- Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.Journal of medicinal chemistry · 2017Article
- A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle.Toxicology research · 2016Article
- Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury.PloS one · 2015Article
- PIRIN2 stabilizes cysteine protease XCP2 and increases susceptibility to the vascular pathogen Ralstonia solanacearum in Arabidopsis.The Plant journal : for cell and molecular biology · 2014Article
- Basal PIR expression in HeLa cells is driven by NRF2 via evolutionary conserved antioxidant response element.Molecular and cellular biochemistry · 2014Article
- Molecular processes that drive cigarette smoke-induced epithelial cell fate of the lung.American journal of respiratory cell and molecular biology · 2014Review
- Article
- Pirin is an iron-dependent redox regulator of NF-κB.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCigarette smoke disrupts the protective barrier established by the airway epithelium through direct damage to the epithelial cells, leading to cell death. Since the morphology of the airway epithelium of smokers does not typically demonstrate necrosis, the most likely mechanism for epithelial cell death in response to cigarette smoke is apoptosis. We hypothesized that cigarette smoke directly up-regulates expression of apoptotic genes, which could play a role in airway epithelial apoptosis.
methodsMicroarray analysis of airway epithelium obtained by bronchoscopy on matched cohorts of 13 phenotypically normal smokers and 9 non-smokers was used to identify specific genes modulated by smoking that were associated with apoptosis. Among the up-regulated apoptotic genes was pirin (3.1-fold, p < 0.002), an iron-binding nuclear protein and transcription cofactor. In vitro studies using human bronchial cells exposed to cigarette smoke extract (CSE) and an adenovirus vector encoding the pirin cDNA (AdPirin) were performed to test the direct effect of cigarette smoke on pirin expression and the effect of pirin expression on apoptosis.
resultsQuantitative TaqMan RT-PCR confirmed a 2-fold increase in pirin expression in the airway epithelium of smokers compared to non-smokers (p < 0.02). CSE applied to primary human bronchial epithelial cell cultures demonstrated that pirin mRNA levels increase in a time-and concentration-dependent manner (p < 0.03, all conditions compared to controls). Overexpression of pirin, using the vector AdPirin, in human bronchial epithelial cells was associated with an increase in the number of apoptotic cells assessed by both TUNEL assay (5-fold, p < 0.01) and ELISA for cytoplasmic nucleosomes (19.3-fold, p < 0.01) compared to control adenovirus vector.
conclusionThese observations suggest that up-regulation of pirin may represent one mechanism by which cigarette smoke induces apoptosis in the airway epithelium, an observation that has implications for the pathogenesis of cigarette smoke-induced diseases.
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