K. Sugahara et al., Differential expression of CCAAT enhancer binding protein family in rat alveolar epithelial cell proliferation and in acute lung injury, CELL TIS RE, 297(2), 1999, pp. 261-270
Although alveolar reorganization after acute lung injury depends on regener
ation of alveolar epithelial cells, there is little knowledge of regulation
of pulmonary healing process. Transcription factors may play key roles in
this regulation. To investigate whether the CCAAT enhancer binding protein
(C/EBP) family, alpha, beta, and delta, were involved in alveolar reorganiz
ation after injury, we examined expression of C/EBP proteins and mRNAs in l
ung injuries induced by lipopolysaccharide (LPS) or bleomycin (Bleo) and in
cell proliferation by keratinocyte growth factor (KGF). By immunohistochem
istry, we demonstrated that C/EBP alpha and C/EBP beta were expressed in al
veolar type II cells and alveolar macrophages, but C/EBP delta was expresse
d restrictedly in some of alveolar type II cells in a spatial pattern in th
e control lungs. Further, these three C/EBP family members were differentia
lly expressed in alveolar cell proliferation and in acute lung injury, in w
hich, interestingly, C/EBP alpha and C/EBP delta were reciprocally expresse
d in alveolar type II cell proliferation and in pulmonary fibrosis. However
, expressions of their mRNAs by in situ hybridization were dramatically inc
reased in the affected lesions of the lungs by LPS and Bleo, and Northern b
lot analysis showed an increased abundance of the mRNA for C/EBP beta in LP
S-treated lungs and for C/EBP delta in Bleo-treated lungs, compared with th
ose in the control lungs. Thus, differential expression of the C/EBP family
may be required to maintain and reorganize the basic integrity of alveolar
structure during pathological states, which suggests an important role for
the C/EBP family in maintaining normal alveolar architecture and function
and in repairing the damaged epithelium after injury.