Human renal mesangial cells are a target for the anti-inflammatory action of 9-cis retinoic acid
Open accessAbstract
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‐α, RAR‐β and RXR‐α increased after incubation with 9‐cRA whereas RXR‐γ was inhibited, suggesting a major role for RARs and RXRs in 9‐cRA‐anti‐inflammatory effects. 9‐cRA was toxic only at 50 μ M (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. British Journal of Pharmacology (2000) 131, 1673–1683; doi:10.1038/sj.bjp.0703728
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- Authors
- Manzano, V. M., Muñoz, J. C. S., Jiménez, J. R., Puyol, M. R., Puyol, D. R., Kitamura, M., & Cazaña, F. J. L.
- Affiliations
- Universidad de Alcalá (ES)
- University College London (GB)
- ORCID
- Kitamura, M
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 131
- Issue
- 8
- Pages
- 1673-1683
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1572488
- OpenAlex
- W2002195410
- Cited by
- 35
- References
- 61
- Citations by year
- 2025: 1 · 2024: 3 · 2021: 5 · 2018: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Comunidad de Madrid
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- 9-cis-retinoic acid, renal mesangial cells, retinoic acid receptor, retinoid X receptor, glomerular inflammation, mesangial cell proliferation, hydrogen peroxide-induced cell death, apoptosis, monocyte adhesion, fibronectin, osteopontin, catalase, glutathione, anti-inflammatory therapy
- MeSH terms
- Alitretinoin, Adult, Anti-Inflammatory Agents, Catalase, Cell Adhesion, Cell Division, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Fibronectins, Gene Expression Regulation, Glomerular Mesangium, Glutathione, Humans, Hydrogen Peroxide, Monocytes, RNA, Messenger, Sialoglycoproteins, Time Factors, Transcription Factors, Tretinoin, Apoptosis, Receptors, Retinoic Acid, Intercellular Adhesion Molecule-1, Coculture Techniques, Vascular Cell Adhesion Molecule-1, Retinoid X Receptors, Osteopontin
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