Elf3 plays a role in regulating bronchiolar epithelial repair kinetics following Clara cell-specific injury

E74-like transcription factor-3 (Elf3), a member of the E26 transformation-specific transcription factor family, is strongly expressed in epithelial-rich tissues, such as small intestine, fetal lung, and various lung cancers. Although previous studies have shown a defect in terminal differentiation of the small intestinal epithelium of Elf3-deficient (Elf3-/-) mice during embryonic development, very little is known about the role Elf3 may play in repair of the airway epithelium after injury. In order to investigate whether Elf3 is involved in regeneration of the bronchiolar epithelium after Clara cell-specific injury, we administered naphthalene to both wild-type (Elf3+/+) and Elf3-/- mice. Histopathological analysis revealed no significant difference in the extent of naphthalene-induced Clara cell necrosis between Elf3+/+ mice and Elf3-/- mice. In the bronchiolar epithelium of Elf3-/- mice, there was a substantial delay in the kinetics of cell proliferation and mitosis along with Clara cell renewal, whereas in the peribronchiolar interstitium, there was a significantly greater level of cell proliferation and mitosis in Elf3-/- mice than in Elf3+/+ mice. Last, the intensity of immunopositive signal for transforming growth factor-beta type II receptor, which is a well-known transcriptional target gene of Elf3 and involved in the induction of epithelial cell differentiation, was significantly lower in the bronchiolar epithelium of Elf3-/- mice when compared with Elf3+/+ mice. Taken together, our results suggest that Elf3 plays an important role in the regulation of lung cell proliferation and differentiation during repair of the injured bronchiolar airway epithelium. Laboratory Investigation (2011) 91, 1514-1529; doi:10.1038/labinvest.2011.100; published online 27 June 2011