Role of E74‐like transcription factor‐3 in the pulmonary regenerative response to naphthalene‐induced bronchiolar epithelial injury

Abstract

E74‐like transcription factor‐3 (Elf‐3), a member of the ETS transcription factor family, is strongly expressed in epithelial‐rich tissues, such as the developing lung and small intestine. Although previous studies have shown a defect in the terminal differentiation of the small intestinal epithelium of Elf‐3‐deficient mice during embryonic development, very little is known about the role Elf‐3 may play in the repair of the lung epithelium after injury. In order to elucidate an involvement of Elf‐3 in regeneration of the bronchiolar epithelium after Clara cell‐specific injury, we administered naphthalene to both wild type (Elf‐3 +/+) and Elf‐3‐deficient (Elf‐3 −/−) mice. Histopathological analysis revealed no significant difference in the extent of naphthalene‐induced Clara cell injury between Elf‐3 +/+ mice and Elf‐3 −/− mice. We found that the kinetics of cell proliferation and mitosis in the distal bronchiolar airway epithelium as well as Clara cell reconstitution was delayed in Elf‐3 −/− mice as compared to Elf‐3 +/+ mice; however, cell proliferation and mitosis in the peribronchiolar interstitium of Elf‐3 −/− mice was significantly greater than that of Elf‐3 +/+ mice after naphthalene treatment. Taken together, our results suggest that Elf‐3 plays an important role in the regulation of lung cell proliferation and differentiation during repair of the injured bronchiolar epithelium.