PMID- 15677312
OWN - NLM
STAT- MEDLINE
DCOM- 20050628
LR  - 20181201
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 16
IP  - 3
DP  - 2005 Mar
TI  - Mechanical stretch induces monocyte chemoattractant activity via an 
      NF-kappaB-dependent monocyte chemoattractant protein-1-mediated pathway in human 
      mesangial cells: inhibition by rosiglitazone.
PG  - 688-96
AB  - Hemodynamic abnormalities are important in the pathogenesis of the glomerular 
      damage in diabetes. Glomerular macrophage infiltration driven by the chemokine 
      monocyte chemoattractant protein-1 (MCP-1) is an early event in diabetic 
      nephropathy. The thiazolidinedione rosiglitazone ameliorates albumin excretion 
      rate in diabetic patients with microalbuminuria and has anti-inflammatory 
      properties, raising the possibility of a relationship between its renoprotective 
      and anti-inflammatory activity. Investigated was whether mesangial cell 
      stretching, mimicking in vitro glomerular capillary hypertension, enhances MCP-1 
      expression and monocyte chemoattractant activity. The effect of the combination 
      of stretch with high glucose on MCP-1 production was studied and, finally, the 
      effect of rosiglitazone on these processes was assessed. Stretching of human 
      mesangial cells significantly enhanced their monocyte chemoattractant activity. 
      This effect was mediated by MCP-1 as it was paralleled by a significant rise in 
      both MCP-1 mRNA and protein levels and was completely abolished by MCP-1 
      blockade. Combined exposure to both stretch and high glucose further increased 
      MCP-1 production. Stretch activated the IkappaB-NF-kappaB pathway, and NF-kappaB 
      inhibition, with the use of the specific inhibitor SN50, completely abolished 
      stretch-induced MCP-1, indicating that stretch-induced MCP-1 was NF-kappaB 
      dependent. The addition of rosiglitazone significantly diminished stretch-induced 
      NF-kappaB activation, MCP-1 production, and monocyte chemotaxis. In conclusion, 
      stretching of mesangial cells stimulates their monocyte chemoattractant activity 
      via an NF-kappaB-mediated, MCP-1-dependent pathway, and this effect is prevented 
      by rosiglitazone.
FAU - Gruden, Gabriella
AU  - Gruden G
AD  - Department of Diabetes and Endocrinology, Cardiovascular Division, King's 
      College, London, UK. ggruden@hotmail.com
FAU - Setti, Giorgia
AU  - Setti G
FAU - Hayward, Anthea
AU  - Hayward A
FAU - Sugden, David
AU  - Sugden D
FAU - Duggan, Sara
AU  - Duggan S
FAU - Burt, Davina
AU  - Burt D
FAU - Buckingham, Robin E
AU  - Buckingham RE
FAU - Gnudi, Luigi
AU  - Gnudi L
FAU - Viberti, Giancarlo
AU  - Viberti G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050126
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Gene Expression/drug effects/physiology
MH  - Glomerular Mesangium/cytology/drug effects/*physiology
MH  - Glucose/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - I-kappa B Proteins/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Rosiglitazone
MH  - Stress, Mechanical
MH  - Thiazolidinediones/*pharmacology
EDAT- 2005/01/29 09:00
MHDA- 2005/06/29 09:00
CRDT- 2005/01/29 09:00
PHST- 2005/01/29 09:00 [pubmed]
PHST- 2005/06/29 09:00 [medline]
PHST- 2005/01/29 09:00 [entrez]
AID - ASN.2004030251 [pii]
AID - 10.1681/ASN.2004030251 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2005 Mar;16(3):688-96. doi: 10.1681/ASN.2004030251. Epub 2005 
      Jan 26.