PMID- 28106723
OWN - NLM
STAT- MEDLINE
DCOM- 20170424
LR  - 20181211
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Jan 17
TI  - Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression 
      Increase and Epithelial Tight Junction Dysfunction in TNF-alpha Treated Cell 
      Monolayers.
LID - 10.3390/ijms18010157 [doi]
LID - 157
AB  - Tight junction dysfunction plays a vital role in some chronic inflammatory 
      diseases. Pro-inflammatory cytokines, especially tumor necrosis factor alpha 
      (TNF-alpha), act as important factors in intestinal epithelial tight junction 
      dysfunction during inflammatory conditions. Autophagy has also been shown to be 
      crucial in tight junction function and claudin-2 expression, but whether 
      autophagy has an effect on the change of claudin-2 expression and tight junction 
      function induced by TNF-alpha is still unknown. To answer this question, we examined 
      the expression of claudin-2 protein, transepithelial electrical resistance (TER), 
      and permeability of cell monolayers, autophagy flux change, and lysosomal pH 
      after TNF-alpha with or without PP242 treatment. Our study showed that claudin-2 
      expression, intestinal permeability, microtubule-associated protein 1 light chain 
      3B II (LC3B-II) and sequestosome 1 (P62) expression largely increased while TER 
      values decreased in TNF-alpha treated cell monolayers. Further research using 
      3-methyladenine (3-MA), bafilomycin A1, and ad-mCherry-GFP-LC3B adenovirus 
      demonstrated that LC3B-II increase induced by TNF-alpha was attributed to the 
      inhibition of autophagic degradation. Moreover, both qualitative and quantitative 
      method confirmed the increase of lysosomal pH, and mammalian target of rapamycin 
      (mTOR) inhibitor PP242 treatment relieved this elevation. Moreover, PP242 
      treatment also alleviated the change of autophagy flux, TER, and claudin-2 
      expression induced by TNF-alpha. Therefore, we conclude that increase of claudin-2 
      levels and intestinal epithelial tight junction dysfunction are partly caused by 
      the inhibition of autophagic degradation in TNF-alpha treated cell monolayers.
FAU - Zhang, Cong
AU  - Zhang C
AD  - Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200092, China. zhang-cong@sjtu.edu.cn.
FAU - Yan, Junkai
AU  - Yan J
AD  - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 
      Institute for Pediatric Research, Shanghai 200092, China. 
      yanjunkai2015@sjtu.edu.cn.
FAU - Xiao, Yongtao
AU  - Xiao Y
AD  - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 
      Institute for Pediatric Research, Shanghai 200092, China. ytxiaocell@163.com.
FAU - Shen, Yujie
AU  - Shen Y
AD  - Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200092, China. shenyujie@sjtu.edu.cn.
FAU - Wang, Jiazheng
AU  - Wang J
AD  - Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200092, China. wangjiazheng1991@163.com.
FAU - Ge, Wensong
AU  - Ge W
AD  - Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200092, China. gewensong@126.com.
FAU - Chen, Yingwei
AU  - Chen Y
AD  - Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200092, China. xinhuachenyw@shsmu.edu.cn.
AD  - Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 
      Institute for Pediatric Research, Shanghai 200092, China. 
      xinhuachenyw@shsmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170117
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Claudin-2)
RN  - 0 (Indoles)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (Macrolides)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Purines)
RN  - 0 (SQSTM1 protein, human)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5142-23-4 (3-methyladenine)
RN  - 88899-55-2 (bafilomycin A1)
RN  - H5669VNZ7V (PP242)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Blotting, Western
MH  - Caco-2 Cells
MH  - Cell Line
MH  - Claudin-2/*metabolism
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Indoles/pharmacology
MH  - Lysosomes/chemistry/metabolism
MH  - Macrolides/pharmacology
MH  - Microscopy, Confocal
MH  - Microtubule-Associated Proteins/metabolism
MH  - Purines/pharmacology
MH  - Rats
MH  - Sequestosome-1 Protein/metabolism
MH  - Tight Junctions/*drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC5297790
OTO - NOTNLM
OT  - TNF-alpha
OT  - autophagy
OT  - barrier function
OT  - claudin-2
OT  - inflammatory
COIS- The authors declare no conflict of interest.
EDAT- 2017/01/21 06:00
MHDA- 2017/04/25 06:00
PMCR- 2017/01/01
CRDT- 2017/01/21 06:00
PHST- 2016/11/23 00:00 [received]
PHST- 2017/01/01 00:00 [revised]
PHST- 2017/01/10 00:00 [accepted]
PHST- 2017/01/21 06:00 [entrez]
PHST- 2017/01/21 06:00 [pubmed]
PHST- 2017/04/25 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - ijms18010157 [pii]
AID - ijms-18-00157 [pii]
AID - 10.3390/ijms18010157 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Jan 17;18(1):157. doi: 10.3390/ijms18010157.