PMID- 31440938
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20220928
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 42
IP  - 6
DP  - 2019 Dec
TI  - GSK-3beta Inhibitor Induces Expression of the TLR4/MyD88/NF-kappaB Signaling Pathway to 
      Protect Against Renal Ischemia-Reperfusion Injury During Rat Kidney 
      Transplantation.
PG  - 2105-2118
LID - 10.1007/s10753-019-01074-2 [doi]
AB  - Ischemia-reperfusion injury (IRI) is an inevitable consequence of kidney 
      transplantation (KT). The aim of our study was to investigate the protective 
      effect of a glycogen synthase kinase 3beta (GSK-3beta) inhibitor against cold IRI in a 
      rat renal transplantation (RT) model and a rat cold-IRI model through the 
      toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear 
      factor kappa-light-chain-enhancer of the activated B cell (NF-kappaB) signaling pathway. 
      We treated Sprague Dawley (SD) rats in the RT and cold-IRI models with 5 mg/kg 
      and 1 mg/kg, respectively, of the GSK-3beta inhibitor 
      4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). We then measured 
      inflammatory factors, i.e., tumor necrosis factor alpha (TNF-alpha) and 
      interleukins-1beta and IL-6 (IL-1beta, IL-6), as well as oxidative stress markers, 
      i.e., superoxide dismutase (SOD) and malondialdehyde (MDA), in serum and kidneys. 
      Renal function tests and pathological examinations were performed at 0, 1, 2, 3, 
      and 7 days after RT or cold IRI. We measured expression of TLR4, MyD88, inhibitor 
      of NF-kappaB kinase (IkappaB), phosphorylated IkappaB (p-IkappaB), NF-kappaB p65, p-p65, GSK-3beta, and 
      phosphorylated GSK-3beta (p-GSK-3beta) by Western blot and immunohistological staining. 
      After intervention with the GSK-3beta inhibitor, renal function was improved; 
      oxidative stress injury was reduced; expression of p-GSK-3beta was upregulated; 
      expression of p-IkappaB, TLR4, MyD88, and p-p65 was downregulated; pathological 
      damage was significantly reduced; and expression of TNF-alpha, IL-1beta, and IL-6 
      messenger ribonucleic acid (mRNA) was downregulated. These results strongly 
      suggested that GSK-3beta might be a key target for the treatment of IRI in KT. The 
      GSK-3beta inhibitor inhibited phosphorylation of NF-kappaB p65 and IkappaB by inhibiting the 
      TLR/MyD88 pathway, reducing oxidative stress injury and the production of 
      downstream inflammatory factors.
FAU - Su, Shuai
AU  - Su S
AD  - Department of Urology, The First Affiliated Hospital of Chongqing Medical 
      University, Yixueyuan Road 1#, Yuzhongqu, Chongqing, 400016, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Forensic Medicine, Hainan Medical University, Haikou, 571199, 
      China.
FAU - Zhang, Qilin
AU  - Zhang Q
AD  - Department of Urology, The First Affiliated Hospital of Chongqing Medical 
      University, Yixueyuan Road 1#, Yuzhongqu, Chongqing, 400016, China.
FAU - Yin, Zhikang
AU  - Yin Z
AD  - Department of Urology, The First Affiliated Hospital of Chongqing Medical 
      University, Yixueyuan Road 1#, Yuzhongqu, Chongqing, 400016, China. 
      yinzhikang2005@sina.com.
LA  - eng
GR  - CSTC2014jcyjA0210/Chongqing Science and Technology Development Foundation/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione)
RN  - 0 (Myd88 protein, rat)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Thiadiazoles)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Animals
MH  - Glycogen Synthase Kinase 3 beta/*antagonists & inhibitors
MH  - Kidney/injuries/pathology
MH  - Kidney Transplantation/*adverse effects
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*prevention & control
MH  - Signal Transduction/*drug effects
MH  - Thiadiazoles/*therapeutic use
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - TLR4/MyD88/NF-kappaB pathway
OT  - glycogen synthase kinase 3beta
OT  - kidney transplantation
OT  - renal ischemia-reperfusion injury
EDAT- 2019/08/24 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/08/24 06:00
PHST- 2019/08/24 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/08/24 06:00 [entrez]
AID - 10.1007/s10753-019-01074-2 [pii]
AID - 10.1007/s10753-019-01074-2 [doi]
PST - ppublish
SO  - Inflammation. 2019 Dec;42(6):2105-2118. doi: 10.1007/s10753-019-01074-2.