Expression of endothelin-1 during Clara cell injury and bronchiolar epithelial repair

L. S. Van Winkle, C. D. Brown, Z. A. Johnson, Charles Plopper

Research output: Contribution to journalArticlepeer-review


Clara cells are primary targets of metabolically activated pulmonary toxicants. The proteins that regulate bronchiolar epithelial repair after Clara cell injury are largely unknown, although members of both the EGF and IGF families are known to increase during repair. Increased endothelin-1 (ET-1) protein is found in diseased lungs. ET-1 stimulates cell proliferation. To determine if altered ET-1 expression correlates with the proliferative phase of bronchiolar epithelial repair after Clara cell injury, we examined the distribution and abundance of ET-1 in the lungs of mice 1-14 days post naphthalene injury (DPI) using immunohistochemistry. Previous studies in this injury model have shown that epithelial cell proliferation is maximal 1-2 DPI, complete 4 DPI and is followed by epithelial re-differentiation (4-14 DPI). In control mice, ET-1 was distributed primarily in the interstitium and matrix closely associated with airways and was detected diffusely in the cuboidal bronchiolar epithelium. At 1-2 DPI, ET-1 deposition increased in attenuated peribronchiolar interstitial cells, airway associated matrix and along the basal surfaces of squamated epithelium in the injury target zone. At 4 DPI, ET-1 distribution shifted to lateral spaces between epithelial cells and to focal points on lateral epithelial cell membranes. The abundant ET-1 previously associated with the basement membrane zone declined but was still present in patches. ET-1 returned to control levels of distribution and abundance 7-14 DPI. We conclude that increased ET-1 protein occurs concurrent to increased cell proliferation during bronchiolar epithelial repair of Clara cell injury.

Original languageEnglish (US)
JournalFASEB Journal
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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