PMID- 18826996 OWN - NLM STAT- MEDLINE DCOM- 20090129 LR - 20220316 IS - 1531-2267 (Electronic) IS - 1094-8341 (Print) IS - 1094-8341 (Linking) VI - 36 IP - 1 DP - 2008 Dec 12 TI - Network analysis of temporal effects of intermittent and sustained hypoxia on rat lungs. PG - 24-34 LID - 10.1152/physiolgenomics.00258.2007 [doi] AB - The molecular networks underlying the lung response to hypoxia are not fully understood. We employed systems biology approaches to study temporal effects of intermittent or sustained hypoxia on gene expression in rat lungs. We obtained gene expression profiles from rats exposed to intermittent or sustained hypoxia lasting 0-30 days and identified differentially expressed genes, their patterns, biological processes, and regulatory networks critical for lung response to intermittent or sustained hypoxia. We validated selected genes with quantitative real-time PCR. Intermittent and sustained hypoxia induced two distinct sets of genes in rat lungs that displayed different temporal expression patterns. Intermittent hypoxia induced genes mostly involved in ion transport and homeostasis, neurological processes, and steroid hormone receptor activity, while sustained hypoxia induced genes principally participating in immune responses. The intermittent hypoxia-activated network suggested a role for cross talk between estrogen receptor 1 (ESR1) and other key proteins in hypoxic responses. The sustained hypoxia-activated network was indicative of vascular remodeling and pulmonary hypertension. We confirmed the temporal expression changes of 12 genes (including the Esr1 gene and 4 ESR1 target genes) in intermittent hypoxia and 8 genes in sustained hypoxia with quantitative real-time PCR. CONCLUSIONS: intermittent and sustained hypoxia induced distinct gene expression patterns in rat lungs. The functional characteristics of genes activated by these two distinct perturbations suggest their roles in the downstream physiological effects of intermittent and sustained hypoxia. Our results demonstrate the discovery potential of applying systems biology approaches to the understanding of mechanisms underlying hypoxic lung response. FAU - Wu, Wei AU - Wu W AD - Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Div. of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. wuw2@upmc.edu FAU - Dave, Nilesh B AU - Dave NB FAU - Yu, Guoying AU - Yu G FAU - Strollo, Patrick J AU - Strollo PJ FAU - Kovkarova-Naumovski, Elizabeta AU - Kovkarova-Naumovski E FAU - Ryter, Stefan W AU - Ryter SW FAU - Reeves, Stephen R AU - Reeves SR FAU - Dayyat, Ehab AU - Dayyat E FAU - Wang, Yang AU - Wang Y FAU - Choi, Augustine M K AU - Choi AM FAU - Gozal, David AU - Gozal D FAU - Kaminski, Naftali AU - Kaminski N LA - eng GR - 1-F32-HL-78164-2/HL/NHLBI NIH HHS/United States GR - HL-65270/HL/NHLBI NIH HHS/United States GR - 2P50-HL-60296-06/HL/NHLBI NIH HHS/United States GR - P50-HL-084932/HL/NHLBI NIH HHS/United States GR - HL-073745/HL/NHLBI NIH HHS/United States GR - HL-0793941/HL/NHLBI NIH HHS/United States GR - HL-69932/HL/NHLBI NIH HHS/United States GR - HL-0894932/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20080930 PL - United States TA - Physiol Genomics JT - Physiological genomics JID - 9815683 RN - 0 (Estrogen Receptor alpha) SB - IM MH - Animals MH - Estrogen Receptor alpha/genetics/metabolism MH - Gene Expression Profiling MH - *Gene Regulatory Networks MH - Hypoxia/*genetics/metabolism MH - Lung/*metabolism MH - Male MH - Microarray Analysis MH - Rats MH - Rats, Sprague-Dawley PMC - PMC2604785 EDAT- 2008/10/02 09:00 MHDA- 2009/01/30 09:00 PMCR- 2009/12/01 CRDT- 2008/10/02 09:00 PHST- 2008/10/02 09:00 [entrez] PHST- 2008/10/02 09:00 [pubmed] PHST- 2009/01/30 09:00 [medline] PHST- 2009/12/01 00:00 [pmc-release] AID - 00258.2007 [pii] AID - PG-00258-2007 [pii] AID - 10.1152/physiolgenomics.00258.2007 [doi] PST - ppublish SO - Physiol Genomics. 2008 Dec 12;36(1):24-34. doi: 10.1152/physiolgenomics.00258.2007. Epub 2008 Sep 30.