PMID- 9848782
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20210518
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 9
IP  - 12
DP  - 1998 Dec
TI  - Hyaluronan induces monocyte chemoattractant protein-1 expression in renal tubular 
      epithelial cells.
PG  - 2283-90
AB  - Hyaluronan (HA) is a nonsulfated glycosaminoglycan that accumulates in the renal 
      interstitium in immune-mediated kidney diseases. The functional significance of 
      such HA deposition in the kidney has not been elucidated. Several studies have 
      suggested that HA may exhibit proinflammatory effects. Since chemokines such as 
      monocyte chemoattractant protein-1 (MCP-1) play an important role in the 
      recruitment of leukocytes in renal injury, this study tested whether HA and its 
      fragments could promote MCP-1 production by renal parenchymal cells. Mouse 
      cortical tubular cells were stimulated with fragmented HA or with high molecular 
      weight HA (Healon) in vitro and were examined for MCP-1 expression. Fragmented 
      HA, but not Healon, increased MCP-1 mRNA within 30 min with a peak after 2 h. In 
      addition, a 10-fold increase of MCP-1 protein in the supernatant was found after 
      a 6-h stimulation with fragmented HA. The enhanced MCP-1 mRNA and protein 
      expression in response to HA was dose-dependent between 1 and 100 microg/ml. 
      Upregulation of MCP-1 protein production could be blocked by preincubation with 
      actinomycin D or cycloheximide, suggesting that MCP-1 mRNA and protein expression 
      in response to HA are based on de novo synthesis. The HA-stimulated MCP-1 
      production was also inhibited with anti-CD44 antibodies, suggesting that MCP-1 is 
      upregulated at least in part by signaling through CD44. In summary, fragmented HA 
      markedly stimulates renal tubular MCP-1 production by mechanisms that involve 
      binding to the HA receptor CD44. It is hypothesized that the accumulation of HA 
      in immune renal injury could participate in the recruitment and activation of 
      inflammatory cells in vivo through production of MCP-1.
FAU - Beck-Schimmer, B
AU  - Beck-Schimmer B
AD  - Physiological Institute, University of Zurich-Irchel, Zurich, Switzerland.
FAU - Oertli, B
AU  - Oertli B
FAU - Pasch, T
AU  - Pasch T
FAU - Wuthrich, R P
AU  - Wuthrich RP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Hyaluronan Receptors)
RN  - 0 (RNA, Messenger)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/drug effects/metabolism
MH  - Extracellular Matrix/*physiology
MH  - Gene Expression Regulation/*drug effects
MH  - Hyaluronan Receptors/drug effects/physiology
MH  - Hyaluronic Acid/administration & dosage/*pharmacology
MH  - Immune Complex Diseases/metabolism/pathology
MH  - Kidney Tubules/cytology/*drug effects
MH  - Mice
MH  - Molecular Weight
MH  - RNA, Messenger/biosynthesis/genetics
EDAT- 1998/12/16 00:00
MHDA- 1998/12/16 00:01
CRDT- 1998/12/16 00:00
PHST- 1998/12/16 00:00 [pubmed]
PHST- 1998/12/16 00:01 [medline]
PHST- 1998/12/16 00:00 [entrez]
AID - 10.1681/ASN.V9122283 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1998 Dec;9(12):2283-90. doi: 10.1681/ASN.V9122283.