PMID- 30476082
OWN - NLM
STAT- MEDLINE
DCOM- 20190613
LR  - 20190613
IS  - 1460-2423 (Electronic)
IS  - 0959-6658 (Linking)
VI  - 29
IP  - 3
DP  - 2019 Mar 1
TI  - Globo-series glycosphingolipids enhance Toll-like receptor 4-mediated 
      inflammation and play a pathophysiological role in diabetic nephropathy.
PG  - 260-268
LID - 10.1093/glycob/cwy105 [doi]
AB  - Alteration of glycosphingolipid (GSL) expression plays key roles in the 
      pathogenesis and pathophysiology of many important human diseases, including 
      cancer, diabetes and glycosphingolipidosis. Inflammatory processes are involved 
      in development and progression of diabetic nephropathy, a major complication of 
      type 2 diabetes mellitus. GSLs are known to play roles in inflammatory responses 
      in various diseases, and levels of renal GSLs are elevated in mouse models of 
      diabetic nephropathy; however, little is known regarding the pathophysiological 
      role of these GSLs in this disease process. We studied proinflammatory activity 
      of GSLs in diabetic nephropathy using spontaneously diabetic mouse strain KK. 
      Mice were fed a high-fat diet (HFD) (60% kcal from fat) or normal diet (ND) (4.6% 
      kcal from fat) for a period of 8 wk. HFD-feeding resulted in quantitative and 
      qualitative changes of renal globo-series GSLs (particularly Gb3Cer), 
      upregulation of TNF-alpha, and induction of renal inflammation. Gb3Cer/Gb4Cer 
      treatment enhanced inflammatory responses via TLR4 in TLR4/MD-2 complex 
      expressing cells, including HEK293T, mouse bone marrow-derived macrophages 
      (BMDMs) and human monocytes. Our findings suggest that HFD-induced increase of 
      Gb3Cer/Gb4Cer positively modulate TLR4-mediated inflammatory response, and that 
      such GSLs play an important pathophysiological role in diabetic nephropathy.
CI  - (c) The Author(s) 2018. Published by Oxford University Press. All rights reserved. 
      For permissions, please e-mail: journals.permissions@oup.com.
FAU - Nitta, Takahiro
AU  - Nitta T
AD  - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, 
      Tohoku Medical and Pharmaceutical University, Sendai, Japan.
AD  - Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of 
      Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, 
      Japan.
FAU - Kanoh, Hirotaka
AU  - Kanoh H
AD  - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, 
      Tohoku Medical and Pharmaceutical University, Sendai, Japan.
FAU - Inamori, Kei-Ichiro
AU  - Inamori KI
AD  - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, 
      Tohoku Medical and Pharmaceutical University, Sendai, Japan.
FAU - Suzuki, Akemi
AU  - Suzuki A
AD  - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, 
      Tohoku Medical and Pharmaceutical University, Sendai, Japan.
FAU - Takahashi, Tomoko
AU  - Takahashi T
AD  - Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of 
      Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, 
      Japan.
FAU - Inokuchi, Jin-Ichi
AU  - Inokuchi JI
AD  - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, 
      Tohoku Medical and Pharmaceutical University, Sendai, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Glycobiology
JT  - Glycobiology
JID - 9104124
RN  - 0 (Glycosphingolipids)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Trihexosylceramides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 71965-57-6 (globotriaosylceramide)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/complications/genetics
MH  - Diabetic Nephropathies/*genetics/metabolism/pathology
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Glycosphingolipids/*genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Inflammation/*genetics/metabolism/pathology
MH  - Kidney/metabolism/pathology
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Signal Transduction/genetics
MH  - Toll-Like Receptor 4/*genetics/metabolism
MH  - Trihexosylceramides/*genetics
MH  - Tumor Necrosis Factor-alpha/genetics
OTO - NOTNLM
OT  - Globo-series GSLs
OT  - TLR4 ligands
OT  - Toll-like receptor 4
OT  - diabetic nephropathy
OT  - renal inflammation
EDAT- 2018/11/27 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/11/27 06:00
PHST- 2018/10/04 00:00 [received]
PHST- 2018/11/14 00:00 [revised]
PHST- 2018/11/21 00:00 [accepted]
PHST- 2018/11/27 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/11/27 06:00 [entrez]
AID - 5199375 [pii]
AID - 10.1093/glycob/cwy105 [doi]
PST - ppublish
SO  - Glycobiology. 2019 Mar 1;29(3):260-268. doi: 10.1093/glycob/cwy105.