Therapeutic effect of all-trans-retinoic acid (at-RA) on an autoimmune nephritis experimental model: Role of the VLA-4 integrin

被引：17

作者：

Escribese M.M. ^{[1
,6
]}

Conde E. ^{[1
]}

Martín A. ^{[2
]}

Sáenz-Morales D. ^{[1
]}

Sancho D. ^{[3
]}

De Lema G.P. ^{[4
]}

Lucio-Cazaña J. ^{[5
]}

Sánchez-Madrid F. ^{[3
]}

García-Bermejo M.L. ^{[1
]}

Mampaso F.M. ^{[1
]}

机构：

[1] Department of Pathology, Hospital Ramón Y Cajal, Universidad de Alcalá, Madrid

[2] Department of Biology, Universidad SEK, Segovia

[3] Department of Immunology, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid

[4] Medizinische Poliklinik der Ludwig Maximillians-Universität, Munich

[5] Department of Physiology, Universidad de Alcalá, Madrid

[6] Dpt. of Microbiology, Mount Sinai School of Medicine, New York, NY

来源：

BMC Nephrology | / 8卷 / 1期

关键词：

Proteinuria; Reverse Transcriptase Polymerase Chain Reaction; Renal Tissue; Brown Norway; Renal Interstitium;

D O I：

10.1186/1471-2369-8-3

中图分类号：

学科分类号：

摘要：

Background. Mercuric chloride (HgCl2) induces an autoimmune nephritis in the Brown Norway (BN) rats characterized by anti-glomerular basement membrane antibodies (anti-GBM Ab) deposition, proteinuria and a severe interstitial nephritis, all evident at day 13 of the disease. We assessed the effects of all-trans retinoic acid (at-RA) in this experimental model. At-RA is a vitamin A metabolite which has shown beneficial effects on several nephropathies, even though no clear targets for at-RA were provided. Methods. We separated animals in four different experimental groups (HgCl2, HgCl2+at-RA, at-RA and vehicle). From each animal we collected, at days 0 and 13, numerous biological samples: urine, to measure proteinuria by colorimetry; blood to determine VLA-4 expression by flow citometry; renal tissue to study the expression of VCAM-1 by Western blot, the presence of cellular infiltrates by immunohistochemistry, the IgG deposition by immunofluorescence, and the cytokines expression by RT-PCR. Additionally, adhesion assays to VCAM-1 were performed using K562 α4 transfectant cells. ANOVA tests were used for statistical significance estimation. Results. We found that at-RA significantly decreased the serum levels of anti-GBM and consequently its deposition along the glomerular membrane. At-RA markedly reduced proteinuria as well as the number of cellular infiltrates in the renal interstitium, the levels of TNF-α and IL-1β cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in an in vivo model that at-RA reduced, to basal levels, the expression of VLA-4 (α4β1) integrin induced by mercury on peripheral blood leukocytes (PBLs). In addition, using K562 α4 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1. Conclusion. Here we demonstrate a therapeutic effect of at-RA on an autoimmune experimental nephritis model in rats. We report a significant reduction of the VLA-4 integrin expression on PBLs as well as the inhibition of the VLA4/VCAM1-dependent leukocyte adhesion by at-RA treatment. Thereby we point out the VLA-4 integrin as a target for at-RA in vivo. © 2007 Escribese et al; licensee BioMed Central Ltd.

引用

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