Upregulation of transcription factors in lung in the early phase of postpneumonectomy lung growth

In the adult rodent, pneumonectomy results in compensatory lung growth char acterized by cell proliferation. The molecular mechanisms governing this re sponse remain unknown. We hypothesized that, in the early period postpneumo nectomy, upregulated expression of transcription factors drives the growth process. We utilized a cDNA expression array to screen for upregulated tran scription factors after left pneumonectomy in adult C57BL/6 mice, using uno perated mice as controls. Quantification of mRNA expression in the remainin g lung at 2 h demonstrated a twofold or greater upregulation of six transcr iption factors: early growth response gene-1 (Egr-1), Nurr77, tristetraprol in, the primary inhibitor of nuclear factor-kappaB (I kappaB-alpha), gut-en riched Kruppel-like factor (GKLF), and LRG-21. Northern analysis was used t o quantify the upregulation of expression of these genes relative to sham t horacotomy and unoperated controls. The largest increase was in Egr-1 (4.7- fold. naive). Time-course analysis over the first 24 h confirmed the transi ent nature of the early upregulation. In the context that postpneumonectomy lung growth is associated with cell proliferation and that genes such as E gr-1, Nurr77, LRG-21, and tristetraprolin have known roles in stress respon se, vascular biology, embryology, and cellular development, these data supp ort the concept that transcription factors function early in the cascade of events leading to the compensatory response.