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Achaete-scute Homologue-1 Tapers Neuroendocrine Cell Differentiation in Lungs After Exposure to Naphthalene

Overview
Journal Toxicol Sci
Specialty Toxicology
Date 2010 Jun 18
PMID 20554700
Citations 5
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Abstract

The basic helix-loop-helix transcription factor achaete-scute homologue-1 (ASH1) plays a critical role in regulating the neuroendocrine (NE) phenotype in normal and neoplastic lung. Transgenic (TG) mice that constitutively express human ASH1 (hASH1) under control of the Clara cell 10-kDa protein (CC10) promoter in non-NE airway lining cells display progressive epithelial hyperplasia and bronchiolar metaplasia or bronchiolization of the alveoli (BOA). However, little is known about the involvement of hASH1 in regeneration of the conducting airway. In this study, we investigated the impact of hASH1 on airway cell injury and repair in the TG mice following an intraperitoneal injection of naphthalene, which specifically ablates bronchiolar Clara cells and induces pulmonary NE cell hyperplasia. We discovered an overall attenuation of NE maturation coupled with increased proliferation in TG mice during post-naphthalene repair. In addition, BOA lesions revealed enhanced epithelial cell proliferation while preserving Clara cell markers CC10 and the principal naphthalene-metabolizing enzyme cytochrome P4502F2. These data suggest that ASH1 may play an important role in maintaining a progenitor phenotype that promotes renewal of both NE and epithelial cells. Moreover, ASH1 may propagate a stem cell microenvironment in BOA where epithelium becomes resistant to naphthalene toxicity.

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References
1.
Mahvi D, BANK H, Harley R . Morphology of a naphthalene-induced bronchiolar lesion. Am J Pathol. 1977; 86(3):558-72. PMC: 2032128. View

2.
Giangreco A, Reynolds S, Stripp B . Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Pathol. 2002; 161(1):173-82. PMC: 1850682. DOI: 10.1016/S0002-9440(10)64169-7. View

3.
Phimister A, Nagasawa H, Buckpitt A, Plopper C . Prevention of naphthalene-induced pulmonary toxicity by glutathione prodrugs: roles for glutathione depletion in adduct formation and cell injury. J Biochem Mol Toxicol. 2005; 19(1):42-51. DOI: 10.1002/jbt.20052. View

4.
Plopper C, Macklin J, Nishio S, Hyde D, Buckpitt A . Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of.... Lab Invest. 1992; 67(5):553-65. View

5.
Van Winkle L, Buckpitt A, Nishio S, Isaac J, Plopper C . Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice. Am J Physiol. 1995; 269(6 Pt 1):L800-18. DOI: 10.1152/ajplung.1995.269.6.L800. View