PMID- 25852733
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150408
LR  - 20200929
IS  - 1664-5529 (Print)
IS  - 1664-5529 (Electronic)
IS  - 1664-5529 (Linking)
VI  - 5
IP  - 1
DP  - 2015 Jan-Apr
TI  - Effects of Tumor Necrosis Factor-alpha on Podocyte Expression of Monocyte 
      Chemoattractant Protein-1 and in Diabetic Nephropathy.
PG  - 1-18
LID - 10.1159/000369576 [doi]
AB  - BACKGROUND/AIMS: Tumor necrosis factor (TNF)-alpha is believed to play a role in 
      diabetic kidney disease. This study explores the specific effects of TNF-alpha with 
      regard to nephropathy-relevant parameters in the podocyte. METHODS: Cultured 
      mouse podocytes were treated with recombinant TNF-alpha and assayed for production of 
      monocyte chemoattractant protein-1 (MCP-1) by enzyme-linked immunosorbent assay 
      (ELISA). TNF-alpha signaling of MCP-1 was elucidated by antibodies against TNF 
      receptor (TNFR) 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-kappaB), 
      phosphatidylinositol 3-kinase (PI3K) or Akt. In vivo studies were done on male 
      db/m and type 2 diabetic db/db mice. Levels of TNF-alpha and MCP-1 were measured by 
      RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and 
      correlated with albuminuria. RESULTS: Podocytes treated with TNF-alpha showed a 
      robust increase ( approximately 900%) in the secretion of MCP-1, induced in a dose- and 
      time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, 
      which was inducible by TNF-alpha ligand, but did not depend on TNFR1. TNF-alpha then 
      proceeded via the NF-kappaB and the PI3K/Akt systems, based on the effectiveness of 
      the inhibitors of those pathways. For in vivo relevance to diabetic kidney 
      disease, TNF-alpha and MCP-1 levels were found to be elevated in the urine of db/db 
      mice but not in the plasma. CONCLUSION: TNF-alpha potently stimulates podocytes to 
      produce MCP-1, utilizing the TNFR2 receptor and the NF-kappaB and PI3K/Akt pathways. 
      Both TNF-alpha and MCP-1 levels were increased in the urine of diabetic db/db mice, 
      correlating with the severity of diabetic albuminuria.
FAU - Chung, Choon Hee
AU  - Chung CH
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA 
      ; Department of Internal Medicine, Yonsei University Wonju College of Medicine, 
      Wonju, Korea.
FAU - Fan, Jingyi
AU  - Fan J
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA 
      ; Pediatric Department, Wuhan University School of Medicine, Zhongnan Affiliated 
      Hospital, Wuhan, P.R. China.
FAU - Lee, Eun Young
AU  - Lee EY
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA 
      ; Department of Internal Medicine, Soonchunhyang University College of Medicine, 
      Cheonan, Korea.
FAU - Kang, Jeong Suk
AU  - Kang JS
AD  - Department of Internal Medicine, Soonchunhyang University College of Medicine, 
      Cheonan, Korea.
FAU - Lee, Seung Joo
AU  - Lee SJ
AD  - Department of Internal Medicine, Soonchunhyang University College of Medicine, 
      Cheonan, Korea.
FAU - Pyagay, Petr E
AU  - Pyagay PE
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA.
FAU - Khoury, Charbel C
AU  - Khoury CC
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA.
FAU - Yeo, Tet-Kin
AU  - Yeo TK
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA.
FAU - Khayat, Mark F
AU  - Khayat MF
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA.
FAU - Wang, Amy
AU  - Wang A
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA.
FAU - Chen, Sheldon
AU  - Chen S
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Ill., USA 
      ; Section of Nephrology, MD Anderson Cancer Center, Houston, Tex., USA.
LA  - eng
GR  - R01 DK044513/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20150204
PL  - Switzerland
TA  - Nephron Extra
JT  - Nephron extra
JID - 101571879
PMC - PMC4369122
OTO - NOTNLM
OT  - Akt or protein kinase B
OT  - Albuminuria
OT  - Diabetic rodent model
OT  - Nuclear factor-kappaB
OT  - Phosphatidylinositol 3-kinase
OT  - TNF receptor 2
EDAT- 2015/04/09 06:00
MHDA- 2015/04/09 06:01
PMCR- 2015/02/04
CRDT- 2015/04/09 06:00
PHST- 2015/04/09 06:00 [entrez]
PHST- 2015/04/09 06:00 [pubmed]
PHST- 2015/04/09 06:01 [medline]
PHST- 2015/02/04 00:00 [pmc-release]
AID - nne-0005-0001 [pii]
AID - 10.1159/000369576 [doi]
PST - epublish
SO  - Nephron Extra. 2015 Feb 4;5(1):1-18. doi: 10.1159/000369576. eCollection 2015 
      Jan-Apr.