PMID- 30779097
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20200708
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 3
DP  - 2019 Feb
TI  - Cellular mechanism of Tbeta4 intervention in liver fibrosis by regulating NF-kappaB 
      signaling pathway.
PG  - 1279-1290
LID - 17023 [pii]
LID - 10.26355/eurrev_201902_17023 [doi]
AB  - OBJECTIVE: To investigate the inhibitory effect of thymosin-beta4 (Tbeta4) on the 
      activation of the human hepatic stellate cell line (HSC-LX2) induced by 
      interleukin (IL)-1beta. MATERIALS AND METHODS: There were 5 groups in this study, 
      i.e., blank control group, negative control group (SI-NC, empty plasmid), model 
      group (20 ng/ml of IL-1beta), siRNA-Tbeta4 knockdown group (IL-1beta and si-Tbeta4) and Tbeta4 
      treatment group (IL-1beta and 1000 ng/ml of Tbeta4). Cell proliferation rate was 
      measured using the Cell Counting Kit-8 (CCK-8) method. The cell cycle change and 
      percentage of apoptotic cells were determined by Propidium Iodide (PI) DNA 
      staining and Annexin V-fluorescein isothiocyanate (FITC) double staining. 
      Cellular nucleic acid levels of p-IKB and nuclear factor-kappa B (NF-kappaB)/p65 
      proteins were measured by fluorescent quantitative Real Time-Polymerase Chain 
      Reaction (RT-PCR). Double immunofluorescence staining and Western blot were used 
      to detect nuclear translocation of NF-kappaB and p65 and levels of cytoplasmic p-IKB 
      protein and nuclear p65 protein. RESULTS: Due to the G0/G1 phase arrest, the 
      number of cells in the Tbeta4 treatment group increased, compared with the model 
      group and the siRNA-Tbeta4 knockdown group (p<0.01). In the same between-group 
      comparison, apoptotic rate in the Tbeta4 treatment group increased significantly 
      (p<0.05). The cellular nucleic acid levels of p-IKB and NF-kappaB/p65 were markedly 
      higher in the model group and the siRNA-Tbeta4 knockdown group than in the blank 
      control group (p<0.01). The cellular nucleic acid levels of p-IKB and NF-kappaB/p65 
      were remarkably lower in the Tbeta4 treatment group than in the siRNA-Tbeta4 knockdown 
      group (p<0.01). The expression levels of NF-kappaB/p65 and NF-kappaB/p50 were 
      significantly lower in the Tbeta4 treatment group. The expression levels of 
      cytoplasmic p-IKB and nuclear NF-kappaB/p65 were lower in the Tbeta4 treatment group 
      than in the model group (p<0.01). CONCLUSIONS: Tbeta4 significantly inhibited 
      IL-1beta-induced HSC-LX2 cell proliferation. The mechanism may involve decreased 
      activation of the NF-kappaB pathway, decreased expression of p-IKB and nuclear 
      translocation of p65. Therefore, Tbeta4 had the effect of reversing liver fibrosis.
FAU - Zhu, Z-X
AU  - Zhu ZX
AD  - Department of Clinical Medicine, Guizhou Medical University, Guiyang, P. R. 
      China. mcw23b@163.com.
FAU - Zhu, L-L
AU  - Zhu LL
FAU - Cheng, Z
AU  - Cheng Z
FAU - Zhao, X-K
AU  - Zhao XK
FAU - Liu, Y-M
AU  - Liu YM
FAU - Fan, L-D
AU  - Fan LD
FAU - Zou, G-L
AU  - Zou GL
FAU - Ouyang, Q-Y
AU  - Ouyang QY
FAU - Cheng, M-L
AU  - Cheng ML
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factor RelA)
RN  - 549LM7U24W (thymosin beta(4))
RN  - 61512-21-8 (Thymosin)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Proliferation/drug effects/genetics
MH  - Gene Knockdown Techniques
MH  - Hepatic Stellate Cells/drug effects/*metabolism/pathology
MH  - Interleukin-1beta/pharmacology
MH  - Liver Cirrhosis/*metabolism/pathology
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Signal Transduction
MH  - Thymosin/genetics/*metabolism/pharmacology
MH  - Transcription Factor RelA/*metabolism
EDAT- 2019/02/20 06:00
MHDA- 2020/07/09 06:00
CRDT- 2019/02/20 06:00
PHST- 2019/02/20 06:00 [entrez]
PHST- 2019/02/20 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
AID - 17023 [pii]
AID - 10.26355/eurrev_201902_17023 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1279-1290. doi: 
      10.26355/eurrev_201902_17023.