PMID- 28554965
OWN - NLM
STAT- MEDLINE
DCOM- 20180314
LR  - 20210109
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 5
IP  - 10
DP  - 2017 May
TI  - Fetuin-A aggravates lipotoxicity in podocytes via interleukin-1 signaling.
PG  - e13287
LID - 10.14814/phy2.13287 [doi]
LID - e13287
AB  - Sterile inflammation is considered critical in the pathogenesis of diabetic 
      nephropathy (DN). Here we show that Fetuin-A (FetA) or lipopolysaccharide (LPS) 
      exacerbate palmitic acid-induced podocyte death, which is associated with a 
      strong induction of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte 
      chemoattractant (KC). Moreover, blockage of TLR4 prevents MCP-1 and KC secretion 
      and attenuates podocyte death induced by palmitic acid alone or combined with 
      FetA. In addition, inhibition of interleukin-1 (IL-1) signaling by anakinra, a 
      recombinant human IL-1Ra, or a murinized anti-IL-1beta antibody attenuates the 
      inflammatory and ultimate cell death response elicited by FetA alone or combined 
      with palmitic acid. In vivo short-term therapy of diabetic DBA/2J mice with an 
      anti-IL1-beta antibody for 4 weeks prevented an increase in serum FetA and 
      considerably decreased urinary tumor necrosis alpha (TNF-alpha), a known risk factor 
      for DN progression. In summary, our results suggest that FetA similarly to LPS 
      leads to an inflammatory response in podocytes, which exacerbates palmitic 
      acid-induced podocyte death and our data imply a critical role for IL-1beta 
      signaling in this process. The study offers the rational for prolonged in vivo 
      studies aimed at testing anti-IL-1beta therapy for prevention and treatment of DN.
CI  - (c) 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of The Physiological Society and the American Physiological Society.
FAU - Orellana, Jana M
AU  - Orellana JM
AD  - Department of Biomedicine, Molecular Nephrology, University Hospital, Basel, 
      Switzerland.
FAU - Kampe, Kapil
AU  - Kampe K
AD  - Department of Biomedicine, Molecular Nephrology, University Hospital, Basel, 
      Switzerland.
FAU - Schulze, Friederike
AU  - Schulze F
AD  - Department of Biomedicine, Diabetes Research, University Hospital, Basel, 
      Switzerland.
FAU - Sieber, Jonas
AU  - Sieber J
AD  - Department of Biomedicine, Molecular Nephrology, University Hospital, Basel, 
      Switzerland.
AD  - Harvard Medical School and Division of Nephrology, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
FAU - Jehle, Andreas W
AU  - Jehle AW
AD  - Department of Biomedicine, Molecular Nephrology, University Hospital, Basel, 
      Switzerland.
AD  - Department of Internal Medicine, Transplantation Immunology and Nephrology, 
      University Hospital, Basel, Switzerland.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Ahsg protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha-2-HS-Glycoprotein)
RN  - 2V16EO95H1 (Palmitic Acid)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Chemokine CCL2/metabolism
MH  - Diabetic Nephropathies/complications/*metabolism
MH  - Inflammation/chemically induced/complications/*metabolism
MH  - Interleukin 1 Receptor Antagonist Protein/administration & dosage
MH  - Interleukin-1/antagonists & inhibitors/*metabolism
MH  - Interleukin-1beta/antagonists & inhibitors/metabolism
MH  - Keratinocytes/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice, Inbred DBA
MH  - Necrosis
MH  - Palmitic Acid/administration & dosage
MH  - Podocytes/drug effects/*metabolism/pathology
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - alpha-2-HS-Glycoprotein/*administration & dosage
PMC - PMC5449566
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Fetuin-A
OT  - free fatty acids
OT  - interleukin-1
OT  - palmitic acid
OT  - toll-like receptor
COIS- The authors have no conflict of interests.
EDAT- 2017/05/31 06:00
MHDA- 2018/03/15 06:00
PMCR- 2017/05/29
CRDT- 2017/05/31 06:00
PHST- 2017/04/24 00:00 [received]
PHST- 2017/04/26 00:00 [accepted]
PHST- 2017/05/31 06:00 [entrez]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2018/03/15 06:00 [medline]
PHST- 2017/05/29 00:00 [pmc-release]
AID - PHY213287 [pii]
AID - 10.14814/phy2.13287 [doi]
PST - ppublish
SO  - Physiol Rep. 2017 May;5(10):e13287. doi: 10.14814/phy2.13287.