PMID- 29156532
OWN - NLM
STAT- MEDLINE
DCOM- 20180807
LR  - 20180807
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 97
DP  - 2018 Jan
TI  - Paclitaxel alleviated liver injury of septic mice by alleviating inflammatory 
      response via microRNA-27a/TAB3/NF-kappaB signaling pathway.
PG  - 1424-1433
LID - S0753-3322(17)34191-4 [pii]
LID - 10.1016/j.biopha.2017.11.003 [doi]
AB  - Excessive inflammatory response and apoptosis play an important role in the 
      sepsis-induced liver injury. Paclitaxel, a diterpene alkaloid of Taxus 
      brevifolia, is widely used as an anti-tumor drug and shows protective effects on 
      acute lung and kidney injury. However, whether it has a protective effect against 
      sepsis-induced liver injury has not been reported. The objective of this study 
      was to investigate the protective effects of paclitaxel in septic liver injury in 
      mice and associated molecular mechanisms. Our results showed that paclitaxel 
      treatment improved LPS-induced liver injury, as evidenced by the reduced 
      aminotransferase activity, histological scores and apoptosis in the liver 
      tissues. This was accompanied by the alleviating of inflammation and oxidative 
      stress, such as decreased levels of tumor necrosis factor alpha (TNF-alpha), 
      interleukin-1 (IL-6) interleukin-1beta (IL-1beta) and malondialdehyde (MDA) and 
      increased levels of superoxide dismutase (SOD) and glutathione peroxidase 
      (GSH-px) in serum and liver tissues. Subsequent microarray and qRT-PCR analysis 
      further showed that miR-27a was significantly decreased in mice with sepsis, 
      which was recovered by paclitaxel pretreatment. Antagomir-miR-27a suppressed the 
      therapeutic effects of paclitaxel in mice liver injury model via promoting 
      inflammatory response. Of note, TAB3, which participated in the activation of the 
      NF-kappaB signaling pathway, was identified as a direct target of miR-27 by 
      luciferase reporter gene assays. Then, we revealed a reverse relationship between 
      miR-27a expression levels and TAB3 mRNA levels in liver tissues from septic mice. 
      Furthermore, paclitaxel treatment significantly decreased the expression of NF-kappaB 
      p65, but increased inhibitor of nuclear factor-kappaB-alpha (IkappaBalpha) protein levels in 
      septic mice, suggesting the inactivation of NF-kappaB signaling pathway. Notably, the 
      inhibitory effects of paclitaxel on NF-kappaB signaling pathway were reversed by 
      antagomir-miR-27a. Our data indicated that paclitaxel significantly attenuated 
      septic induced liver injury through reducing inflammatory response via 
      miR-27a/TAB3/NF-kappaB signaling pathway.
CI  - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.
FAU - Yang, Qiu
AU  - Yang Q
AD  - Department of Gastroenterology, Second Clinical Medical College of Jinan 
      University, Shenzhen People's Hospital, China.
FAU - Zhang, Dongshan
AU  - Zhang D
AD  - Departments of Emergency Medicine and Nephrology, Second Xiangya Hospital, 
      Central South University, China.
FAU - Li, Ya
AU  - Li Y
AD  - Department of Nephrology, Second Clinical Medical College of Jinan University, 
      Shenzhen People's Hospital, China.
FAU - Li, Yongquan
AU  - Li Y
AD  - Department of Nephrology, Second Clinical Medical College of Jinan University, 
      Shenzhen People's Hospital, China.
FAU - Li, Yinpeng
AU  - Li Y
AD  - Department of Gastroenterology, Second Clinical Medical College of Jinan 
      University, Shenzhen People's Hospital, China. Electronic address: 
      li_yinpeng65@163.com.
LA  - eng
PT  - Journal Article
DEP - 20171214
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn27 microRNA, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tab3 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis/*drug effects
MH  - Disease Models, Animal
MH  - Inflammation/*drug therapy/etiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/metabolism
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/drug effects
MH  - Paclitaxel/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Sepsis/complications/*drug therapy
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Inflammatory response
OT  - MicroRNA-27a
OT  - NF-kappaB signaling pathway
OT  - Paclitaxel
OT  - Sepsis
EDAT- 2017/11/22 06:00
MHDA- 2018/08/08 06:00
CRDT- 2017/11/22 06:00
PHST- 2017/08/16 00:00 [received]
PHST- 2017/10/28 00:00 [revised]
PHST- 2017/11/03 00:00 [accepted]
PHST- 2017/11/22 06:00 [pubmed]
PHST- 2018/08/08 06:00 [medline]
PHST- 2017/11/22 06:00 [entrez]
AID - S0753-3322(17)34191-4 [pii]
AID - 10.1016/j.biopha.2017.11.003 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2018 Jan;97:1424-1433. doi: 10.1016/j.biopha.2017.11.003. 
      Epub 2017 Dec 14.