The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Authors: Yen, Seiha; Preissner, Melissa; Bennett, Ellen; Dubsky, Stephen; Carnibella, Richard; O'Toole, Ronan; Roddam, Louise; Jones, Heather; Dargaville, Peter A.; Fouras, Andreas; Zosky, Graeme R.
Abstract
The aim of this study was to assess the association between regional tidal volume (VT), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB/c mice (n = 8 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional VT and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.e., specific [s]VT and specific [s]FRC). RNA concentrations of 21 genes in 10 different lung regions were quantified using a quantitative PCR array. sFRC at baseline varied regionally, independent of ventilation strategy, whereas sVT varied regionally depending on ventilation strategy. The expression of IL-6 (P = 0.04), Ccl2 (P < 0.01), and Ang-2 (P < 0.05) was associated with sVT but not sFRC. The expression of seven other genes varied regionally (IL-1/3 and RAGE [receptor for advanced glycation end products]) or depended on ventilation strategy (Nfe2l2 [nuclear factor erythroid-derived 2 factor 2], c-fos, and Wnt1) or both (TNF-alpha and Cxcl2), but it was not associated with regional sFRC or 5VT. These observations suggest that regional inflammatory responses to mechanical ventilation are driven primarily by tidal stretch.
Cold stress initiates the Nrf2/UGT1A1/L-FABP signaling pathway in chickens
POULTRY SCIENCE
Authors: Chen, X. Y.; Li, R.; Geng, Z. Y.
Abstract
Cold stress triggers an anti-oxidative response in animals regulated by Nrf2 (nuclear factor 2-like, NFE2L2) binding to deoxyribonucleic acid-regulatory sequences near stress-responsive genes. To identify chicken Nrf2-regulated genes, 3 genetically related experimental groups (EG) with 40 Huainan partridge chickens in each group were chosen. The chickens were maintained at 20 degrees C environmental temperature from 5 wk of age. At 6 wk of age, 10 chickens from each EG were still maintained at 20 degrees C as control, and the other 30 chickens from each EG were exposed to 6 +/- 2 degrees C. Liver samples were collected from the control and from chickens exposed to 6 +/- 2 degrees C for 12, 24, and 72 h for co-immuno-precipitation (CoIP) analysis. Chromatin immunoprecipitation (ChIP)-sequencing experiment in liver cells treated with Dimethyl fumarate (DMF) were carried out. A de novo motif was discovered which closely matched the core Nrf2 consensus binding motif. Genes involved in de novo motif discovery were further analyzed for their enrichment in the anti-oxidative response pathway and the lipid anabolism pathway. There were 14 genes found which are related to oxidative stress. To examine the downstream factors of the 14 responsive genes, one of them, UGT1A1 (UDP glucuronosyltransferase), was further analyzed by CoIP experiment and nano LC-ESI-MS/MS analysis. It was detected that fatty acid-binding protein (L-FABP, 127 AA) might be the potential UGT1A1 downstream interaction proteins. In conclusion, it is proposed that chickens under cold stress generate anti-oxidative stress and thus trigger the Nrf2/ARE signaling pathway, which further up-regulates the expression of L-FABP to inactivate lipid peroxidation of the cell membrane and promote fatty acid storage against the cold environment.