Bcl-2 sustains increased mucous and epithelial cell numbers in metaplastic airway epithelium.

نویسندگان

  • J Foster Harris
  • Mark J Fischer
  • Jon R Hotchkiss
  • Brett P Monia
  • Scott H Randell
  • Jack R Harkema
  • Yohannes Tesfaigzi
چکیده

Bcl-2, an inhibitor of apoptosis, is expressed in LPS-induced metaplastic goblet cells of rat airways. The present study investigated expression of Bcl-2 in airway mucous cells of persons with cystic fibrosis and tested in rats and mice whether its expression is responsible for sustaining metaplastic mucous cells. A significantly higher percentage of mucous cells expressed Bcl-2 in humans with cystic fibrosis compared with control subjects with no disease or subjects with other diseases. In LPS-instilled F344/N rats, the percentage of Bcl-2-positive mucous cells was decreased to background levels before the resolution of goblet cell metaplasia. Furthermore, intraperitoneal injection of rats with antisense oligonucleotides significantly reduced Bcl-2 expression and goblet cell metaplasia in nasal and pulmonary airway epithelia in rats. In contrast, sustained expression of Bcl-2 in transgenic mice by a metallothionein promoter caused increased LPS-induced goblet cell metaplasia over 8 days compared with wild-type mice. These studies demonstrate that Bcl-2 expression sustains goblet cell metaplasia in various species, that epithelial cell numbers are directly linked to the regulation of the numbers of goblet cells, and that downregulating Bcl-2 expression reduces goblet cell metaplasia.

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عنوان ژورنال:
  • American journal of respiratory and critical care medicine

دوره 171 7  شماره 

صفحات  -

تاریخ انتشار 2005