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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2006-05, Vol.290 (5), p.L880-L889
• Main Authors: Zhang, Quiyang, Moe, Orson W, Garcia, Joseph A, Hsia, Connie C. W
• Format: Article
• Language: English
• Subjects: Aging; Animals; Animals, Newborn; Base Sequence; Cloning, Molecular; DNA Primers; Dogs; Gene Expression Regulation, Developmental; Hypoxia-Inducible Factor 1 - genetics; Lung - embryology; Lung - growth & development; Models, Animal; Reverse Transcriptase Polymerase Chain Reaction; RNA, Ribosomal, 18S - genetics; Transcription, Genetic
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00213.2005

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 Address for reprint requests and other correspondence: C. C. W. Hsia, Pulmonary and Critical Care Medicine, Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034