Project Title Mucosal Hypoxia Inducible Factor in Acute Lung Injury Project Summary Over the last decades, convincing evidence has demonstrated a central role of hypoxia inducible factor (HIF) in mammalian oxygen homeostasis. As such, HIF-driven responses are tailored towards adaptation to limited oxygen availability and restoring adequate tissue oxygen levels. More recently, several studies also implicated HIF in transcriptional coordination of inflammatory responses. However, the role of HIF during acute lung injury (ALI) is unknown. Preliminary data from stretch exposure of pulmonary epithelia demonstrates HIF stabilization in vitro. Moreover, in vivo studies of ALI show a protective role of epithelial HIF signaling. Therefore, we hypothesize that HIF-1 is stabilized during ALI, and dampens lung inflammation and tissue injury.
Three specific aims were designed to address novel roles for HIF in ALI. In the first aim, we propose to study mechanisms of mucosal HIF stabilization during cyclic mechanical stretch exposure in vitro, or during ALI in vivo. In the second aim, we will study the role of mucosal HIF in regulating lung inflammation and leukocyte trafficking during ALI. In the third aim, we will study the role of mucosal HIF during the resolution phase of ALI. These studies will shed new light on endogenous pathways that regulate lung inflammation and pulmonary injury. Targeting such pathways will lay the groundwork for novel and specific therapeutic approaches in the treatment of ALI, which are urgently needed to improve morbidity and mortality of critical illness. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Lung Injury, Repair, and Remodeling Study Section (LIRR)
Program Officer
Harabin, Andrea L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Lim, Grace; Facco, Francesca L; Nathan, Naveen et al. (2018) A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes. Anesthesiology 129:192-215
Kiers, Dorien; Wielockx, Ben; Peters, Esther et al. (2018) Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation. EBioMedicine 33:144-156
Yuan, Xiaoyi; Lee, Jae W; Bowser, Jessica L et al. (2018) Targeting Hypoxia Signaling for Perioperative Organ Injury. Anesth Analg 126:308-321
Hoegl, Sandra; Burns, Nana; Angulo, Martín et al. (2018) Capturing the multifactorial nature of ARDS - ""Two-hit"" approach to model murine acute lung injury. Physiol Rep 6:e13648
Bowser, Jessica L; Phan, Luan H; Eltzschig, Holger K (2018) The Hypoxia-Adenosine Link during Intestinal Inflammation. J Immunol 200:897-907
Kork, Felix; Eltzschig, Holger K (2017) The Devil Is in the Detail: Remote Ischemic Preconditioning for Perioperative Kidney Protection. Anesthesiology 126:763-765
Hoegl, Sandra; Ehrentraut, Heidi; Brodsky, Kelley S et al. (2017) NK cells regulate CXCR2+ neutrophil recruitment during acute lung injury. J Leukoc Biol 101:471-480
Neudecker, Viola; Haneklaus, Moritz; Jensen, Owen et al. (2017) Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome. J Exp Med 214:1737-1752
Kork, F; Balzer, F; Krannich, A et al. (2017) Back-calculating baseline creatinine overestimates prevalence of acute kidney injury with poor sensitivity. Acta Physiol (Oxf) 219:613-624
Varadarajan, Supraja G; Kong, Jennifer H; Phan, Keith D et al. (2017) Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord. Neuron 94:790-799.e3

Showing the most recent 10 out of 92 publications