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This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/L880    most recent 00213.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Zhang, Q. Articles by Hsia, C. C. W. Search for Related Content PubMed PubMed Citation Articles by Zhang, Q. Articles by Hsia, C. C. W.

Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas

Submitted 16 May 2005 ; accepted in final form 19 December 2005

We previously found increased expression of erythropoietin receptor (EPO-R) in peripheral dog lung during postnatal and postpneumonectomy (PNX) lung growth. To study the upstream regulation of EPO-R, we analyzed the expression of hypoxia-inducible factors (HIF)-1, -2, and -3 during postnatal lung growth in immature and mature (2.5 and 12 mo old, respectively) dogs and during compensatory lung growth 3 wk and 10 mo after right PNX. Relative to their respective controls, HIF-1 transcript was 52–95% higher in immature lungs and 284% higher in the remaining lung 3 wk post-PNX. HIF-2 transcript did not change during maturation but was 42% lower 3 wk post-PNX. HIF-3 transcript was 53–65% lower in both the immature lung and 3 wk post-PNX. Changes were no longer detectable 10 mo post-PNX. No change in HIF transcripts was observed in kidney and liver post-PNX. Consistent with the mRNA changes, HIF-1 protein was 120 and 196% higher in growing lungs and 3 wk post-PNX relative to their respective controls. Overexpression of HIF-1 in cultured HEK-293 cells increased endogenous expression of EPO-R protein. These results demonstrate regulated expression of the HIF system and parallel changes in HIF-1 and EPO-R expression during two types of lung growth. Because the normal growing lung is not hypoxic, the HIF system likely responds to other signals encountered during sustained lung strain.

hypoxia-inducible factors; pneumonectomy; postnatal development; lung growth; ribonucleic acid blot; real-time polymerase chain reaction; immunoblot

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