PMID- 26061548
OWN - NLM
STAT- MEDLINE
DCOM- 20160713
LR  - 20181113
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 88
IP  - 4
DP  - 2015 Oct
TI  - Macrophage-derived tumor necrosis factor-alpha mediates diabetic renal injury.
PG  - 722-33
LID - 10.1038/ki.2015.162 [doi]
AB  - Monocyte/macrophage recruitment correlates strongly with the progression of 
      diabetic nephropathy. Tumor necrosis factor-alpha (TNF-alpha) is produced by 
      monocytes/macrophages but the direct role of TNF-alpha and/or macrophage-derived 
      TNF-alpha in the progression of diabetic nephropathy remains unclear. Here we tested 
      whether inhibition of TNF-alpha confers kidney protection in diabetic nephropathy via 
      a macrophage-derived TNF-alpha-dependent pathway. Compared to vehicle-treated mice, 
      blockade of TNF-alpha with a murine anti-TNF-alpha antibody conferred kidney protection 
      in Ins2(Akita) mice as indicated by reductions in albuminuria, plasma creatinine, 
      histopathologic changes, kidney macrophage recruitment, and plasma inflammatory 
      cytokine levels at 18 weeks of age. To assess the direct role of 
      macrophage-derived TNF-alpha in diabetic nephropathy, we generated 
      macrophage-specific TNF-alpha-deficient mice (CD11b(Cre)/TNF-alpha(Flox/Flox)). 
      Conditional ablation of TNF-alpha in macrophages significantly reduced albuminuria, 
      the increase in plasma creatinine and blood urea nitrogen, histopathologic 
      changes, and kidney macrophage recruitment compared to diabetic TNF-alpha(Flox/Flox) 
      control mice after 12 weeks of streptozotocin-induced diabetes. Thus, production 
      of TNF-alpha by macrophages plays a major role in diabetic renal injury. Hence, 
      blocking TNF-alpha could be a novel therapeutic approach for treatment of diabetic 
      nephropathy.
FAU - Awad, Alaa S
AU  - Awad AS
AD  - Department of Medicine, Penn State University College of Medicine, Hershey, 
      Pennsylvania, USA.
FAU - You, Hanning
AU  - You H
AD  - Department of Medicine, Penn State University College of Medicine, Hershey, 
      Pennsylvania, USA.
FAU - Gao, Ting
AU  - Gao T
AD  - Department of Medicine, Penn State University College of Medicine, Hershey, 
      Pennsylvania, USA.
FAU - Cooper, Timothy K
AU  - Cooper TK
AD  - Department of Comparative Medicine, Penn State University College of Medicine, 
      Hershey, Pennsylvania, USA.
FAU - Nedospasov, Sergei A
AU  - Nedospasov SA
AD  - Engelhardt Institute of Molecular Biology and Lomonosov Moscow State University, 
      Moscow, Russia.
FAU - Vacher, Jean
AU  - Vacher J
AD  - Clinical Research Institute of Montreal, Department de Medecine, Universite de 
      Montreal, Montreal, Quebec, Canada.
FAU - Wilkinson, Patrick F
AU  - Wilkinson PF
AD  - Department of Immunology Research, Janssen R&D, Spring House, Pennsylvania, USA.
FAU - Farrell, Francis X
AU  - Farrell FX
AD  - Department of Immunology Research, Janssen R&D, Spring House, Pennsylvania, USA.
FAU - Brian Reeves, W
AU  - Brian Reeves W
AD  - Department of Medicine, Penn State University College of Medicine, Hershey, 
      Pennsylvania, USA.
LA  - eng
GR  - DK081876/DK/NIDDK NIH HHS/United States
GR  - R01 DK094930/DK/NIDDK NIH HHS/United States
GR  - R01 DK081876/DK/NIDDK NIH HHS/United States
GR  - DK094930/DK/NIDDK NIH HHS/United States
GR  - DK094930S1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150610
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Biomarkers)
RN  - 0 (CD11b Antigen)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
CIN - Kidney Int. 2015 Oct;88(4):662-5. PMID: 26422621
MH  - Albuminuria/genetics/metabolism/prevention & control
MH  - Animals
MH  - Antibodies, Neutralizing/pharmacology
MH  - Biomarkers/blood
MH  - Blood Urea Nitrogen
MH  - CD11b Antigen/genetics/metabolism
MH  - Chemotaxis
MH  - Creatinine/blood
MH  - Diabetes Mellitus, Experimental/complications/genetics/metabolism
MH  - Diabetic Nephropathies/genetics/*metabolism/pathology/prevention & control
MH  - Genetic Predisposition to Disease
MH  - Inflammation Mediators/antagonists & inhibitors/*metabolism
MH  - Kidney/drug effects/*metabolism/pathology
MH  - Macrophages, Peritoneal/drug effects/*metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Phenotype
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/antagonists & 
      inhibitors/deficiency/genetics/*metabolism
PMC - PMC4589442
MID - NIHMS690109
EDAT- 2015/06/11 06:00
MHDA- 2016/07/14 06:00
PMCR- 2016/04/01
CRDT- 2015/06/11 06:00
PHST- 2014/12/11 00:00 [received]
PHST- 2015/03/24 00:00 [revised]
PHST- 2015/04/09 00:00 [accepted]
PHST- 2015/06/11 06:00 [entrez]
PHST- 2015/06/11 06:00 [pubmed]
PHST- 2016/07/14 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - S2157-1716(15)32248-6 [pii]
AID - 10.1038/ki.2015.162 [doi]
PST - ppublish
SO  - Kidney Int. 2015 Oct;88(4):722-33. doi: 10.1038/ki.2015.162. Epub 2015 Jun 10.