PMID- 29950141
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20200930
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 17
IP  - 11
DP  - 2018
TI  - TNF-alpha induces autophagy through ERK1/2 pathway to regulate apoptosis in neonatal 
      necrotizing enterocolitis model cells IEC-6.
PG  - 1390-1402
LID - 10.1080/15384101.2018.1482150 [doi]
AB  - Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature 
      neonates. Tumor necrosis factor-alpha (TNF-alpha) and autophagy are associated with the 
      pathogenesis of NEC. This study aimed to explore whether TNF-alpha might regulate 
      apoptosis in neonatal NEC model cells IEC-6 via regulation of autophagy. NEC rat 
      model was induced by hand feeding and exposure to asphyxia/cold-stress for 
      histologic examination. The NEC in vitro model (IEC-6/NEC cells) was established 
      by stimulating the intestinal epithelial cell line IEC-6 with lipopolysaccharide 
      (LPS, 100 mug/mL) for 3 h to investigate the effects of TNF-alpha on IEC-6 
      proliferation and apoptosis. In this study, NEC rats showed decreased 
      proliferating cell nuclear antigen (PCNA) expression, increased TUNEL-positive 
      cells, higher expression of TNF-alpha, p-ERK1/2, and autophagy-related proteins in 
      rat small intestine compared with their controls. Additionally, the 
      LPS-stimulated IEC-6/NEC cells showed a significantly decreased proliferation and 
      increased apoptosis compared with the control cells. Furthermore, the 
      LPS-stimulated IEC-6/NEC cells exhibited enhanced autophagy level, as evidenced 
      by a dose-dependent increase in Beclin-1 protein expression, LC3II/LC3I ratio and 
      accumulation of MDC-positive autophagic vacuoles. Moreover, inhibition of 
      autophagy by wortmannin or LY294002 significantly abolished the LPS-mediated 
      decreased proliferation and increased apoptosis of IEC-6/NEC cells. Results also 
      showed that inhibition of ERK1/2 pathway using U0126 significantly inhibited 
      TNF-alpha-induced autophagy. Furthermore, the TNF-alpha-mediated inhibition of IEC-6 
      proliferation and promotion of IEC-6 apoptosis was abolished by U0126. Our 
      findings demonstrated that TNF-alpha might induce autophagy through ERK1/2 pathway to 
      regulate apoptosis in neonatal NEC cells IEC-6. Our study enhances our 
      understanding of neonatal NEC pathogenesis.
FAU - Yuan, Yuhang
AU  - Yuan Y
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Ding, Daokui
AU  - Ding D
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Zhang, Ning
AU  - Zhang N
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Xia, Ziqiang
AU  - Xia Z
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Wang, Jiaxiang
AU  - Wang J
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Yang, Heying
AU  - Yang H
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Guo, Fei
AU  - Guo F
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
FAU - Li, Bing
AU  - Li B
AD  - a Department of Pediatric Surgery , The First Affiliated Hospital of Zhengzhou 
      University , Zhengzhou , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180723
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - *Apoptosis
MH  - *Autophagy
MH  - Cell Line
MH  - Cell Proliferation
MH  - Enterocolitis, Necrotizing/*enzymology/*pathology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Intestine, Small/pathology
MH  - *MAP Kinase Signaling System/drug effects
MH  - *Models, Biological
MH  - Phosphorylation
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC6110600
OTO - NOTNLM
OT  - IEC-6
OT  - TNF-alpha
OT  - apoptosis
OT  - autophagy
OT  - neonatal necrotizing enterocolitis
EDAT- 2018/06/29 06:00
MHDA- 2019/10/29 06:00
PMCR- 2019/07/23
CRDT- 2018/06/29 06:00
PHST- 2018/06/29 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2018/06/29 06:00 [entrez]
PHST- 2019/07/23 00:00 [pmc-release]
AID - 1482150 [pii]
AID - 10.1080/15384101.2018.1482150 [doi]
PST - ppublish
SO  - Cell Cycle. 2018;17(11):1390-1402. doi: 10.1080/15384101.2018.1482150. Epub 2018 
      Jul 23.