PMID- 11139446
OWN - NLM
STAT- MEDLINE
DCOM- 20010222
LR  - 20181130
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 131
IP  - 8
DP  - 2000 Dec
TI  - Human renal mesangial cells are a target for the anti-inflammatory action of 
      9-cis retinoic acid.
PG  - 1673-83
AB  - Mesangial cells play an active role in the inflammatory response to glomerular 
      injury. We have studied in cultured human mesangial cells (CHMC) several effects 
      of 9-cis retinoic acid (9-cRA), an activator of both retinoic acid receptors 
      (RARs) and retinoid X receptors (RXRs). 9-cRA inhibited foetal calf serum-induced 
      CHMC proliferation. It also prevented CHMC death induced by the inflammatory 
      mediator H(2)O(2). This preventive effect was not due to any increase in H(2)O(2) 
      catabolism and it persisted even when both catalase and glutathione synthesis 
      were inhibited. Finally, 9-cRA diminished monocyte adhesion to FCS-stimulated 
      CHMC. Interestingly, the retinoid also inhibited in FCS-stimulated cells the 
      protein expression of two mesangial adhesion molecules, fibronectin and 
      osteopontin, but it did not modify the protein expression of intercellular 
      adhesion molecule-1 and vascular adhesion molecule-1. All major RARs and RXRs 
      isotypes were expressed in CHMC regardless of the presence or absence of 9-cRA. 
      Transcripts to RAR-alpha, RAR-beta and RXR-alpha increased after incubation with 
      9-cRA whereas RXR-gamma was inhibited, suggesting a major role for RARs and RXRs 
      in 9-cRA-anti-inflammatory effects. 9-cRA was toxic only at 50 microM (a 
      concentration 50 - 5000 times higher than required for the effects above). Cell 
      death occurred by apoptosis, whose onset was associated with a pronounced 
      increase in catalase activity and reduced glutathione content, being more 
      effectively induced by all-trans retinoic acid. Modulation of the 
      oxidant/antioxidant balance failed to inhibit apoptosis. We conclude that 
      mesangial cells might be a target for the treatment of inflammatory 
      glomerulopathies with 9-cRA.
FAU - Manzano, V M
AU  - Manzano VM
AD  - Department of Physiology, University of Alcala, Alcala de Henares, Madrid, Spain.
FAU - Munoz, J C
AU  - Munoz JC
FAU - Jimenez, J R
AU  - Jimenez JR
FAU - Puyol, M R
AU  - Puyol MR
FAU - Puyol, D R
AU  - Puyol DR
FAU - Kitamura, M
AU  - Kitamura M
FAU - Cazana, F J
AU  - Cazana FJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Fibronectins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (SPP1 protein, human)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 106441-73-0 (Osteopontin)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Adult
MH  - Alitretinoin
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Catalase/drug effects/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Fibronectins/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Glomerular Mesangium/cytology/*drug effects/metabolism
MH  - Glutathione/drug effects/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Monocytes/cytology
MH  - Osteopontin
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Receptors, Retinoic Acid/genetics
MH  - Retinoid X Receptors
MH  - Sialoglycoproteins/genetics
MH  - Time Factors
MH  - Transcription Factors/genetics
MH  - Tretinoin/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/genetics
PMC - PMC1572488
EDAT- 2001/01/05 11:00
MHDA- 2001/03/03 10:01
PMCR- 2001/12/01
CRDT- 2001/01/05 11:00
PHST- 2001/01/05 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/05 11:00 [entrez]
PHST- 2001/12/01 00:00 [pmc-release]
AID - 0703728 [pii]
AID - 10.1038/sj.bjp.0703728 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2000 Dec;131(8):1673-83. doi: 10.1038/sj.bjp.0703728.