Rat gastric gelatinase induction during endotoxemia.
Despite continued investigation, the pathogenesis of tissue injury secondary to sepsis remains elusive. Further evaluation of the mechanisms by which endotoxemia and sepsis induce tissue injury is necessary to formulate rational and effective treatment strategies. The purpose of these studies was to evaluate the role of the matrix metalloproteinases MMP-2 and MMP-9 in gastric injury during lipopolysaccharide induced endotoxemia. Lipopolysaccharide increased gastric gelatinase activity as determined by in situ and gelatin zymography. Specifically, lipopolysaccharide induced MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) transcription, with subsequent increases in MMP-2 and TIMP-1 protein expression. Furthermore, selective metalloproteinase inhibition ameliorated gastric injury in this model. These data suggest that lipopolysaccharide-induced gastric injury is mediated, at least in part, by increased MMP-2 production.
Robinson
Emily K
EK
Department of Surgery, The University of Texas Health Science Center at Houston, Houston, Texas, USA. emily.k.robinson@uth.tmc.edu
West
Sonlee D
SD
Garay
Alian
A
Mercer
David W
DW
D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D015153:Blotting, Western; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000201:enzymology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology*; D018093:Gelatinases / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013272:Stomach Diseases / Q000473:pathology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9