PMID- 15930146
OWN - NLM
STAT- MEDLINE
DCOM- 20051019
LR  - 20220311
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 289
IP  - 4
DP  - 2005 Oct
TI  - TGF-beta1 stimulates monocyte chemoattractant protein-1 expression in mesangial 
      cells through a phosphodiesterase isoenzyme 4-dependent process.
PG  - C959-70
AB  - Monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor 
      (TGF)-beta1 are critical mediators of renal injury by promoting excessive 
      inflammation and extracellular matrix deposition, thereby contributing to 
      progressive renal disease. In renal disease models, MCP-1 stimulates the 
      production of TGF-beta1. However, a potential role for TGF-beta1 in the 
      regulation of MCP-1 production by mesangial cells (MCs) has not previously been 
      evaluated. The objectives of this study were to define the role of TGF-beta1 in 
      regulation of MCP-1 expression in cultured MCs and to define mechanisms through 
      which rolipram (Rp), a phosphodiesterase isoenzyme 4 (PDE4) inhibitor with 
      anti-inflammatory properties, alters MCP-1 expression. TGF-beta1 induced MCP-1 in 
      a time- and dose-dependent manner without increasing transcription of the MCP-1 
      gene. TGF-beta1-mediated induction of MCP-1 occurred without activation of the 
      NF-kappaB pathway. Rp blocked TGF-beta1-stimulated MCP-1 expression via a protein 
      kinase A-dependent process, at least in part, by decreasing MCP-1 message 
      stability. Rp exerted no effect on activation of the Smad pathway by TGF-beta1. 
      TGF-beta1-mediated induction of MCP-1 required activation of ERK and p38, both of 
      which were suppressed by a PDE4 inhibitor. TGF-beta1-stimulated reactive oxygen 
      species (ROS) generation by MCs, and Rp inhibited ROS generation in 
      TGF-beta1-stimulated MCs; in addition, both Rp and ROS scavengers blocked 
      TGF-beta1-stimulated MCP-1 expression. We conclude that TGF-beta1 stimulates 
      MCP-1 expression through pathways involving activation of ERK, p38, and ROS 
      generation. Positive cross-talk between TGF-beta1 and MCP-1 signaling in MCs may 
      underlie the development of progressive renal disease. Rp, by preventing 
      TGF-beta1-stimulated MCP-1 production, may offer a therapeutic approach in 
      retarding the progression of renal disease.
FAU - Cheng, Jingfei
AU  - Cheng J
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 
      200 First St. SW, Stabile 7, Rochester, Minnesota 55905, USA.
FAU - Diaz Encarnacion, Montserrat M
AU  - Diaz Encarnacion MM
FAU - Warner, Gina M
AU  - Warner GM
FAU - Gray, Catherine E
AU  - Gray CE
FAU - Nath, Karl A
AU  - Nath KA
FAU - Grande, Joseph P
AU  - Grande JP
LA  - eng
GR  - R01 DK-16105/DK/NIDDK NIH HHS/United States
GR  - R01 DK-47060/DK/NIDDK NIH HHS/United States
GR  - R01 DK-55603/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050601
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression
MH  - Glomerular Mesangium/cytology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/*physiology
MH  - Transforming Growth Factor beta1
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2005/06/03 09:00
MHDA- 2005/10/20 09:00
CRDT- 2005/06/03 09:00
PHST- 2005/06/03 09:00 [pubmed]
PHST- 2005/10/20 09:00 [medline]
PHST- 2005/06/03 09:00 [entrez]
AID - 00153.2005 [pii]
AID - 10.1152/ajpcell.00153.2005 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2005 Oct;289(4):C959-70. doi: 
      10.1152/ajpcell.00153.2005. Epub 2005 Jun 1.