PMID- 28322790
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20211008
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 486
IP  - 2
DP  - 2017 Apr 29
TI  - Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-alpha-induced MCP-1 
      expression by modulating p38 and JNK signaling pathways in human renal cortical 
      epithelial cells.
PG  - 499-505
LID - S0006-291X(17)30537-5 [pii]
LID - 10.1016/j.bbrc.2017.03.071 [doi]
AB  - Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are 
      produced predominantly by gut microbiota fermentation of dietary fiber. SCFAs are 
      newly identified as endogenous ligands of two orphan G protein-coupled receptors, 
      GPR41 and GPR43, which have the potential to modulate inflammation. Therefore, 
      GPR41 and GPR43 may mediate the link between the gut microbiome status and 
      various disease conditions including renal inflammation. This study aimed at 
      investigating whether SCFAs activate GPR41 and GPR43, and thereby exert 
      anti-inflammatory effects in human renal cortical epithelial cells (HRCEs) as a 
      main component of kidney tissue. Immunohistochemical analyses of human renal 
      biopsy specimens revealed the expression of GPR41 and GPR43 protein in the distal 
      renal tubules and collecting tubules. TNF-alpha increased the expression of monocyte 
      chemoattractant protein-1 (MCP-1), a potential fibrotic inducer, at least partly 
      via enhancing phosphorylation of p38 and JNK in HRCEs. SCFAs, especially 
      propionate, attenuated TNF-alpha- stimulated MCP-1 expression by inhibiting the 
      phosphorylation of p38 and JNK. This inhibitory effect was considerably 
      attenuated by an inactivator of the Gi/o-type G protein and a Gbetagamma (i/o) blocker, 
      but not by a Galpha (i/o) blocker. Furthermore, SCFA-mediated inhibition of MCP-1 
      expression was significantly blocked by siRNA-induced gene silencing of GPR41 and 
      GPR43. In conclusion, SCFAs lowered TNF-alpha-induced MCP-1 expression by reducing 
      phosphorylation of p38 and JNK in a GPR41/43-dependent manner in HRCEs, 
      suggesting that SCFA modification may be a new therapeutic tool for preventing 
      progression of renal inflammation and fibrosis.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Kobayashi, Mamiko
AU  - Kobayashi M
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Mikami, Daisuke
AU  - Mikami D
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan. Electronic address: dmikami@u-fukui.ac.jp.
FAU - Kimura, Hideki
AU  - Kimura H
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan; Department of Clinical Laboratory, University of Fukui Hospital, 
      Fukui, Japan.
FAU - Kamiyama, Kazuko
AU  - Kamiyama K
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Morikawa, Yukie
AU  - Morikawa Y
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Yokoi, Seiji
AU  - Yokoi S
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Kasuno, Kenji
AU  - Kasuno K
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Takahashi, Naoki
AU  - Takahashi N
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
FAU - Taniguchi, Takanobu
AU  - Taniguchi T
AD  - Division of Cellular Signal Transduction, Department of Biochemistry, Asahikawa 
      Medical University, Asahikawa, Japan.
FAU - Iwano, Masayuki
AU  - Iwano M
AD  - Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 
      Fukui, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170318
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (FFA2R protein, human)
RN  - 0 (FFAR3 protein, human)
RN  - 0 (Fatty Acids, Volatile)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Epithelial Cells/*drug effects/metabolism/pathology
MH  - Fatty Acids, Volatile/metabolism/*pharmacology
MH  - Gene Expression Regulation
MH  - Glomerulonephritis/genetics/metabolism/pathology
MH  - Humans
MH  - Kidney Cortex/drug effects/metabolism/pathology
MH  - Kidney Tubules, Collecting/metabolism/pathology
MH  - MAP Kinase Kinase 4/*genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Receptors, Cell Surface/*genetics/metabolism
MH  - Receptors, G-Protein-Coupled/*genetics/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*genetics/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*genetics/metabolism
OTO - NOTNLM
OT  - GPR41
OT  - GPR43
OT  - JNK
OT  - Monocyte chemoattractant protein-1
OT  - SCFA
OT  - p38
EDAT- 2017/03/23 06:00
MHDA- 2017/06/06 06:00
CRDT- 2017/03/22 06:00
PHST- 2017/03/13 00:00 [received]
PHST- 2017/03/16 00:00 [accepted]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2017/03/22 06:00 [entrez]
AID - S0006-291X(17)30537-5 [pii]
AID - 10.1016/j.bbrc.2017.03.071 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Apr 29;486(2):499-505. doi: 
      10.1016/j.bbrc.2017.03.071. Epub 2017 Mar 18.