Differential expression, time course and distribution of four PARs in rats with endotoxin-induced acute lung injury.
The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. Male Wistar rats were rendered endotoxemic by intra-peritoneal injection of LPS (15 mg/kg body weight). We examined the expression of protein and mRNA and the immunohistochemical localization of PAR isoforms in lung tissues 1, 3, 6, and 10 h after LPS administration. Induction of ALI by LPS was confirmed based on histopathological changes. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. While the time course of PAR-1 and -2 expressions were different, those of PAR-3 and -4 were almost similar. An immunohistochemical analysis showed localization of PAR isoforms in the vascular endothelium, alveolar epithelium, and alveolar macrophages. However, the cellular distribution patterns of PAR isoforms were different. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. The differential expression patterns (over a time course) and distribution of PAR isoforms suggests a distinct role for each isoform in the pathogenesis of LPS-induced ALI.
Jesmin
Subrina
S
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060, Japan.
Gando
Satoshi
S
Zaedi
Sohel
S
Sakuraya
Fumika
F
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000097:blood / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000235:genetics / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; D018179:Receptors, Thrombin; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; C105295:protease-activated receptor 3; D005337:Fibrin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C112908:protease-activated receptor 4; D010100:Oxygen