PMID- 23759023
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220330
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 11
DP  - 2013 Jun 9
TI  - Dexmedetomidine protects against renal ischemia and reperfusion injury by 
      inhibiting the JAK/STAT signaling activation.
PG  - 141
LID - 10.1186/1479-5876-11-141 [doi]
AB  - BACKGROUND: The alpha2-adrenoreceptor agonist dexmedetomidine is known to provide 
      renoprotection against ischemia and reperfusion (I/R) injury. However the 
      underlying molecular mechanisms remain unclear. The purpose of this study was to 
      investigate whether the Janus kinase and signal transducer and activator of 
      transcription (JAK/STAT) signaling pathway plays a role in dexmedetomidine's 
      renoprotection. METHODS: I/R model was induced by bilateral renal pedicle 
      clamping for 45 min followed by 48 h of reperfusion in male Wistar rat. Sham 
      laparotomy served as controls. Animals received dexmedetomidine (50 mug/kg, i.p.) 
      in the absence or presence of atipamezole (250 mug/kg, i.p.), or vehicle (DMSO) in 
      the absence or presence of selective JAK2 inhibitor tyrphostin AG490 (10 mg/kg, 
      i.p.) before ischemia. Renal function, histology, apoptosis, expression of 
      cleaved caspase 3 protein, intercellular adhesion molecule-1 (ICAM-1), monocyte 
      chemoattractant protein-1 (MCP-1) and phosphorylations of JAK2, STAT1 and STAT3 
      were assessed. RESULTS: The animals treated with either dexmedetomidine or AG490 
      exhibited an improved renal functional recovery, attenuated histological lesions 
      and reduced number of apoptotic tubular epithelial cells. Either dexmedetomidine 
      or AG490 inhibited the phosphorylations of JAK2 and its downstream molecule STAT1 
      and STAT3, accompanied by down-regulation the expression of cleaved caspase 3, 
      ICAM-1 and MCP-1 proteins, and significantly ameliorated renal I/R injury. 
      CONCLUSIONS: Dexmedetomidine protects kidney against I/R injury, at least in 
      part, through its inhibitory effects on injury-induced activation of JAK/STAT 
      signaling pathway. If our data can be extrapolated to clinical setting, then 
      dexmedetomidine may therefore serve as a clinical strategy to treat/prevent 
      perioperative renal I/R injury.
FAU - Si, Yanna
AU  - Si Y
FAU - Bao, Hongguang
AU  - Bao H
FAU - Han, Liu
AU  - Han L
FAU - Shi, Hongwei
AU  - Shi H
FAU - Zhang, Yuan
AU  - Zhang Y
FAU - Xu, Li
AU  - Xu L
FAU - Liu, Chenhui
AU  - Liu C
FAU - Wang, Jinsong
AU  - Wang J
FAU - Yang, Xiaobing
AU  - Yang X
FAU - Vohra, Akbar
AU  - Vohra A
FAU - Ma, Daqing
AU  - Ma D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130609
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Protective Agents)
RN  - 0 (STAT Transcription Factors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - Chemokine CCL2/blood
MH  - Dexmedetomidine/pharmacology/*therapeutic use
MH  - Epithelial Cells/drug effects/pathology
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Janus Kinases/*metabolism
MH  - Kidney/drug effects/*pathology/physiopathology
MH  - Kidney Function Tests
MH  - Kidney Tubules/drug effects/pathology
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Rats, Wistar
MH  - Reperfusion Injury/blood/*drug therapy/physiopathology/*prevention & control
MH  - STAT Transcription Factors/*metabolism
MH  - Signal Transduction/drug effects
PMC - PMC3700850
EDAT- 2013/06/14 06:00
MHDA- 2015/03/31 06:00
PMCR- 2013/06/09
CRDT- 2013/06/14 06:00
PHST- 2013/03/10 00:00 [received]
PHST- 2013/05/22 00:00 [accepted]
PHST- 2013/06/14 06:00 [entrez]
PHST- 2013/06/14 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2013/06/09 00:00 [pmc-release]
AID - 1479-5876-11-141 [pii]
AID - 10.1186/1479-5876-11-141 [doi]
PST - epublish
SO  - J Transl Med. 2013 Jun 9;11:141. doi: 10.1186/1479-5876-11-141.