[Role of Janus kinase/signal transducer and activator of transcription pathway in mediating mRNA expression of high mobility group box1 protein in the liver in septic rats].
OBJECTIVE
To investigate the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in mediating mRNA expression of high mobility group box 1 protein (HMGB1) in the liver in septic rats.


METHODS
Using a sepsis model of cecal ligation and puncture (CLP), 98 male Wistar rats were randomly divided into normal control group (n=10), CLP group (n=40), AG490 treatment group (n=24), and Rapamycin (RPM) treatment group (n=24). At serial time points animals in each group were sacrificed, and blood as well as hepatic tissue samples were harvested to determine HMGB1 mRNA expression and serum aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents.


RESULTS
Compared with normal controls, HMGB1 mRNA levels were significantly increased in the liver during 6-48 hours after CLP (P<0.01), and serum AST and ALT contents were significantly elevated at different time points respectively (P<0.05 or P<0.01). Treatment with AG490 and RPM could markedly inhibit HMGB1 mRNA expression in the liver at 24 hours, 48 hours, 6 hours and 24 hours after CLP, respectively. In addition, compared to CLP group, serum AST and ALT contents in both treatment groups could be markedly reduced at various intervals after CLP (P<0.05 or P<0.01).


CONCLUSIONS
These data suggest that the activation of JAK/STAT pathway might be involved in mediating up-regulation of HMGB1 mRNA expression in the liver in CLP-induced sepsis. Treatment with inhibitors of JAK/STAT pathway could markedly down-regulate HMGB1 mRNA expression and attenuate acute liver injury associated with sepsis.
Wang
Song-bai
SB
Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
Yao
Yong-ming
YM
Dong
Ning
N
Yu
Yan
Y
Tao
Guo-cai
GC
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001224:Aspartic Acid / Q000097:blood; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000627:therapeutic use; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D020032:Tyrphostins / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D024243:HMGB1 Protein; D012333:RNA, Messenger; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D001224:Aspartic Acid; D000410:Alanine Transaminase; D011505:Protein-Tyrosine Kinases; D020123:Sirolimus