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1 Division of Pulmonary and Critical Care Medicine, 3 Belfer Gene Therapy Core Facility, and 4 Institute of Genetic Medicine, Weill Medical College of Cornell University, New York, New York 10021; and 2 Divison of Cardiothoracic Surgery, Evanston Northwestern Healthcare, Evanston, Illinois 60202
In the adult rodent,
pneumonectomy results in compensatory lung growth characterized by cell
proliferation. The molecular mechanisms governing this response remain
unknown. We hypothesized that, in the early period postpneumonectomy,
upregulated expression of transcription factors drives the growth
process. We utilized a cDNA expression array to screen for upregulated
transcription factors after left pneumonectomy in adult C57BL/6 mice,
using unoperated mice as controls. Quantification of mRNA expression in
the remaining lung at 2 h demonstrated a twofold or greater upregulation of six transcription factors: early growth response gene-1
(Egr-1), Nurr77, tristetraprolin, the primary inhibitor of nuclear
factor-
B (IB-
), gut-enriched Krüppel-like factor (GKLF), and LRG-21. Northern analysis was used to quantify the upregulation of expression of these genes relative to sham thoracotomy and unoperated controls. The largest increase was in Egr-1
(4.7-fold > naive). Time-course analysis over the first 24 h
confirmed the transient nature of the early upregulation. In the
context that postpneumonectomy lung growth is associated with cell
proliferation and that genes such as Egr-1, Nurr77, LRG-21, and
tristetraprolin have known roles in stress response, vascular biology,
embryology, and cellular development, these data support the concept
that transcription factors function early in the cascade of events leading to the compensatory response.
pneumonectomy; postpneumonectomy compensatory response
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