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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We separated animals in four different experimental groups (HgCl<jats:sub>2<\/jats:sub>, HgCl<jats:sub>2<\/jats:sub>+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 \u03b14 transfectant cells. ANOVA tests were used for statistical significance estimation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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-\u03b1 and IL-1\u03b2 cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in an<jats:italic>in vivo<\/jats:italic>model that at-RA reduced, to basal levels, the expression of VLA-4 (\u03b14\u03b21) integrin induced by mercury on peripheral blood leukocytes (PBLs). In addition, using K562 \u03b14 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2369-8-3","type":"journal-article","created":{"date-parts":[[2007,1,25]],"date-time":"2007-01-25T04:23:37Z","timestamp":1169699017000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Therapeutic effect of all-trans-retinoic acid (at-RA) on an autoimmune nephritis experimental model: role of the VLA-4 integrin"],"prefix":"10.1186","volume":"8","author":[{"given":"Mar\u00eda M","family":"Escribese","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Conde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"S\u00e1enz-Morales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Sancho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo P\u00e9rez","family":"de Lema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Lucio-Caza\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"S\u00e1nchez-Madrid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda L","family":"Garc\u00eda-Bermejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco M","family":"Mampaso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,1,24]]},"reference":[{"key":"79_CR1","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.4049\/jimmunol.137.8.2548","volume":"137","author":"L Pelletier","year":"1986","unstructured":"Pelletier L, Paquier R, Hirsh F, Sapin C, Druet P: Autoreactive T cells in mercury-induced autoimmune disease: in vitro demonstration. 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