{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:22:26Z","timestamp":1790907746413,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2005,11,30]],"date-time":"2005-11-30T00:00:00Z","timestamp":1133308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine whether the platelet\u2010derived growth factor (PDGF) receptor antagonist imatinib ameliorates glomerulonephritis in MRL\/<jats:italic>lpr<\/jats:italic> mice, a condition that is similar to severe lupus nephritis in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen\u2010week\u2010old MRL\/<jats:italic>lpr<\/jats:italic> female mice having an advanced stage of glomerulonephritis were divided into 3 groups according to treatment: 1) 50 mg\/kg or 2) 10 mg\/kg of imatinib (administered orally 4 times a week up to 24 weeks of age) or 3) vehicle solution (untreated group). The histopathologic condition of the kidneys and salivary glands of each mouse as well as the cumulative survival rates, extent of lymphadenopathy and splenomegaly, and serum chemistry and immunologic values were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In mice treated with 50 mg\/kg imatinib, neither proliferation of glomerular cells nor crescent formation occurred. A drastic decrease in mesangial matrix was noted. Mice treated with 50 mg\/kg imatinib had a prolonged life span compared with mice treated with 10 mg\/kg imatinib and untreated mice. Expression of PDGF receptor and transforming growth factor \u03b2 messenger RNA in the kidneys was significantly reduced in the 50 mg\/kg imatinib\u2013treated mice compared with that in the 10 mg\/kg imatinib\u2013treated mice (<jats:italic>P<\/jats:italic> &lt; 0.05) and the untreated mice (<jats:italic>P<\/jats:italic> &lt; 0.01). Intriguingly, lymphadenopathy and salivary gland inflammation were also attenuated in imatinib\u2010treated mice, in a dose\u2010dependent manner. Serum levels of IgG and anti\u2013double\u2010stranded DNA antibodies were also reduced in the imatinib\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicate that imatinib has a pleiotropic therapeutic effect, namely, the inhibition of PDGF signaling and immunosuppression, on the glomerulonephritis of MRL\/<jats:italic>lpr<\/jats:italic> mice, which suggests a potential application of this drug in the treatment of human lupus nephritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.21424","type":"journal-article","created":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T17:29:20Z","timestamp":1133458160000},"page":"3987-3996","source":"Crossref","is-referenced-by-count":56,"title":["Amelioration of autoimmune nephritis by imatinib in MRL\/<i>lpr<\/i> 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