PMID- 19420107
OWN - NLM
STAT- MEDLINE
DCOM- 20090820
LR  - 20211020
IS  - 1522-1466 (Electronic)
IS  - 0363-6127 (Print)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 1
DP  - 2009 Jul
TI  - The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-beta, 
      increases podocyte motility and albumin permeability.
PG  - F85-94
LID - 10.1152/ajprenal.90642.2008 [doi]
AB  - The role of monocyte chemoattractant protein-1 (MCP-1) in diabetic nephropathy is 
      typically viewed through the lens of inflammation, but MCP-1 might exert 
      noninflammatory effects on the kidney cells directly. Glomerular podocytes in 
      culture, verified to express the marker nephrin, were exposed to diabetic 
      mediators such as high glucose or angiotensin II and assayed for MCP-1. Only 
      transforming growth factor-beta (TGF-beta) significantly increased MCP-1 
      production, which was prevented by SB431542 and LY294002, indicating that 
      signaling proceeded through the TGF-beta type I receptor kinase and the 
      phosphatidylinositol 3-kinase pathway. The TGF-beta-induced MCP-1 was found to 
      activate the podocyte's cysteine-cysteine chemokine receptor 2 (CCR2) and, as a 
      result, enhance the cellular motility, cause rearrangement of the actin 
      cytoskeleton, and increase podocyte permeability to albumin in a Transwell assay. 
      The preceding effects of TGF-beta were replicated by treatment with recombinant 
      MCP-1 and blocked by a neutralizing anti-MCP-1 antibody or a specific CCR2 
      inhibitor, RS102895. In conclusion, this is the first description that TGF-beta 
      signaling through PI3K induces the podocyte expression of MCP-1 that can then 
      operate via CCR2 to increase cellular migration and alter albumin permeability 
      characteristics. The pleiotropic effects of MCP-1 on the resident kidney cells 
      such as the podocyte may exacerbate the disease process of diabetic albuminuria.
FAU - Lee, Eun Young
AU  - Lee EY
AD  - Division of Nephrology/Hypertension, Northwestern University, Chicago, Illinois 
      60611, USA.
FAU - Chung, Choon Hee
AU  - Chung CH
FAU - Khoury, Charbel C
AU  - Khoury CC
FAU - Yeo, Tet Kin
AU  - Yeo TK
FAU - Pyagay, Petr E
AU  - Pyagay PE
FAU - Wang, Amy
AU  - Wang A
FAU - Chen, Sheldon
AU  - Chen S
LA  - eng
GR  - R01-DK-044513/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 - 20090506
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Albumins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Albumins/*metabolism
MH  - Albuminuria/metabolism/physiopathology
MH  - Animals
MH  - Cell Membrane Permeability/drug effects/*physiology
MH  - Cell Movement/drug effects/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Cytoskeleton/metabolism
MH  - Disease Models, Animal
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Podocytes/cytology/drug effects/*metabolism
MH  - Receptors, CCR2/*metabolism
MH  - Signal Transduction/physiology
MH  - Transforming Growth Factor beta/*metabolism/pharmacology
PMC - PMC2711714
EDAT- 2009/05/08 09:00
MHDA- 2009/08/21 09:00
PMCR- 2010/07/01
CRDT- 2009/05/08 09:00
PHST- 2009/05/08 09:00 [entrez]
PHST- 2009/05/08 09:00 [pubmed]
PHST- 2009/08/21 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 90642.2008 [pii]
AID - F-90642-2008 [pii]
AID - 10.1152/ajprenal.90642.2008 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Jul;297(1):F85-94. doi: 
      10.1152/ajprenal.90642.2008. Epub 2009 May 6.