Proteomic analysis of naphthalene-induced airway epithelial injury and repair in a cystic fibrosis mouse model.
Combined results from laser capture microdissection of mouse airway epithelial cells followed by high power (MALDI-FTICR) MS, and fluorescent two-dimensional gel elctrophoresis (2D-DIGE) of the whole lung, allowed us to identify proteins differentially expressed after naphthalene induced airway injury. Further, we discovered several novel aspects of Cystic Fibrosis (CF) lung pathology in an F508del-Cftr mouse model using this approach. The combined MALDI-FTICR-MS and 2D-DIGE data show that lung carbonyl reductase (CBR2), involved in prostaglandin metabolism, converting PGE2 to PGF2alpha, is localized to airway cells and is reduced 2-fold in mutant mice compared to normal, both before and after challenge. Further, we observe a downregulation of two key enzymes of retinoic acid metabolism after injury, which is more pronounced in CF mutant mice. These data show that state-of-the-art proteomics can be used to evaluate airway injury in small cell samples. Further, the results suggest the involvement of prostaglandin and retinoic acid metabolism in the abnormal responses of CF mutant mice to injury.
Department of Cell Biology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Isabel M
IM
Carvalho-Oliveira
Nuno
N
Charro
Jamil
J
Aarbiou
Ruvalic M
RM
Buijs-Offerman
Martina
M
Wilke
Thomas
T
Schettgen
Thomas
T
Kraus
Mark K
MK
Titulaer
Peter
P
Burgers
Theo M
TM
Luider
Deborah
D
Penque
Bob J
BJ
Scholte
D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR / Q000378:metabolism; D008822:Mice, Transgenic; D009281:Naphthalenes / Q000494:pharmacology; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D020545:Respiratory Mucosa / Q000473:pathology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014212:Tretinoin / Q000378:metabolism
D009281:Naphthalenes; D020543:Proteome; C031721:naphthalene; D014212:Tretinoin