Xeroderma pigmentosum group C deficiency alters cigarette smoke DNA damage cell fate and accelerates emphysema development

Catherine R. Sears, Huaxin Zhou, Matthew J. Justice, Amanda J. Fisher, Jacob Saliba, Isaac Lamb, Jessica Wicker, Kelly S. Schweitzer, Irina Petrache

Research output: Contribution to journalEditorial

8 Scopus citations

Abstract

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

Original languageEnglish (US)
Pages (from-to)402-411
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume58
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Apoptosis
  • Autophagy
  • Chronic obstructive lung disease
  • Xeroderma pigmentosum

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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