PMID- 24361893
OWN - NLM
STAT- MEDLINE
DCOM- 20140319
LR  - 20220409
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 443
IP  - 3
DP  - 2014 Jan 17
TI  - Pro-inflammatory/Th1 gene expression shift in high glucose stimulated mesangial 
      cells and tubular epithelial cells.
PG  - 969-74
LID - S0006-291X(13)02141-4 [pii]
LID - 10.1016/j.bbrc.2013.12.072 [doi]
AB  - Diabetic nephropathy (DN) is a major cause of end stage kidney disease and a 
      strong risk factor for cardiovascular diseases. Growing data show chronic 
      inflammation plays an important role for the progression of DN. As for the immune 
      cells, anti-inflammatory leukocytes as well as pro-inflammatory leukocytes play 
      an important role in DN. In addition to leukocytes, renal resident cells 
      contribute to the inflammatory process of DN. However, precise functions, 
      phenotypes and immune balance of renal resident cells remain to be explored. 
      Therefore, we hypothesized that the aberrant immune balance of renal resident 
      cells contributes to the pathogenesis of DN. To explore this possibility, we 
      performed genome-wide transcriptome profiling in mesangial cells and tubular 
      epithelial cells (TECs), which were stimulated by high glucose (HG) and detected 
      the expression of inflammation associated genes. HG increased the mRNA expression 
      of oxidative stress, inflammasome and mammalian target of rapamycin (mTOR) 
      related genes in mesangial cells. Pro-inflammatory/Th1 gene expression was 
      upregulated, but Th2 related gene expression was downregulated in mesangial 
      cells. In TECs, HG stimulation increased pro-inflammatory/Th1/Th2 gene 
      expression. Phosphorylation of signaling proteins shifted towards 
      pro-inflammatory phenotype with suppressed phosphorylation of Th2 related 
      signaling in TECs. The data taken together indicate that HG shifts the immune 
      balance toward pro-inflammatory/Th1 phenotype in mesangial cells and TECs, which 
      might initiate and/or prolong inflammation, thereby resulting in diabetic 
      nephropathy.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Iwata, Yasunori
AU  - Iwata Y
AD  - Division of Infection Control, Kanazawa University, Japan; Division of 
      Nephrology, Kanazawa University, Japan. Electronic address: iwata-knz@umin.ac.jp.
FAU - Furuichi, Kengo
AU  - Furuichi K
AD  - Division of Nephrology, Kanazawa University, Japan; Division of Blood 
      Purification, Kanazawa University, Japan.
FAU - Hashimoto, Shinichi
AU  - Hashimoto S
AD  - Department of Laboratory Medicine, Kanazawa University, Japan; Department of 
      Molecular Preventive Medicine, University of Tokyo, Tokyo, Japan.
FAU - Yokota, Kiyonobu
AU  - Yokota K
AD  - Department of Laboratory Medicine, Kanazawa University, Japan.
FAU - Yasuda, Haruka
AU  - Yasuda H
AD  - Department of Laboratory Medicine, Kanazawa University, Japan.
FAU - Sakai, Norihiko
AU  - Sakai N
AD  - Division of Nephrology, Kanazawa University, Japan; Division of Blood 
      Purification, Kanazawa University, Japan.
FAU - Kitajima, Shinji
AU  - Kitajima S
AD  - Division of Nephrology, Kanazawa University, Japan; Department of Disease Control 
      and Homeostasis, Kanazawa University, Japan.
FAU - Toyama, Tadashi
AU  - Toyama T
AD  - Division of Nephrology, Kanazawa University, Japan; Department of Disease Control 
      and Homeostasis, Kanazawa University, Japan.
FAU - Shinozaki, Yasuyuki
AU  - Shinozaki Y
AD  - Division of Nephrology, Kanazawa University, Japan; Department of Laboratory 
      Medicine, Kanazawa University, Japan.
FAU - Sagara, Akihiro
AU  - Sagara A
AD  - Division of Nephrology, Kanazawa University, Japan; Department of Disease Control 
      and Homeostasis, Kanazawa University, Japan.
FAU - Matsushima, Kouji
AU  - Matsushima K
AD  - Department of Molecular Preventive Medicine, University of Tokyo, Tokyo, Japan.
FAU - Kaneko, Shuichi
AU  - Kaneko S
AD  - Department of Disease Control and Homeostasis, Kanazawa University, Japan.
FAU - Wada, Takashi
AU  - Wada T
AD  - Division of Nephrology, Kanazawa University, Japan; Department of Laboratory 
      Medicine, Kanazawa University, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131219
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Chemokines)
RN  - 0 (Inflammasomes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytokine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Line
MH  - Chemokines/genetics/metabolism
MH  - Epithelial Cells/*metabolism/pathology
MH  - Gene Expression Regulation/*drug effects
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Inflammasomes/metabolism
MH  - Inflammation/*genetics/pathology
MH  - Intracellular Space/drug effects/metabolism
MH  - Kidney Tubules/*pathology
MH  - Mesangial Cells/*metabolism/pathology
MH  - Oxidative Stress/drug effects/genetics
MH  - Phenotype
MH  - Phosphorylation/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Cytokine/genetics/metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Th1 Cells/drug effects/*metabolism
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Genome-wide analysis
OT  - Inflammation
OT  - Mesangial cells
OT  - Tubular epithelial cells
EDAT- 2013/12/24 06:00
MHDA- 2014/03/22 06:00
CRDT- 2013/12/24 06:00
PHST- 2013/11/28 00:00 [received]
PHST- 2013/12/14 00:00 [accepted]
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/03/22 06:00 [medline]
AID - S0006-291X(13)02141-4 [pii]
AID - 10.1016/j.bbrc.2013.12.072 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2014 Jan 17;443(3):969-74. doi: 
      10.1016/j.bbrc.2013.12.072. Epub 2013 Dec 19.