2009
DOI: 10.1681/asn.2008010036
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Imatinib Suppresses Cryoglobulinemia and Secondary Membranoproliferative Glomerulonephritis

Abstract: Imatinib is a receptor tyrosine kinase inhibitor that blocks the activity of c-Abl, c-Kit, and PDGF receptors. We tested the protective effects of imatinib in thymic stromal lymphopoietin transgenic mice, a model of cryoglobulinemia and associated membranoproliferative glomerulonephritis (MPGN), in which some glomerular manifestations likely result from PDGF receptor activation. Surprising, administration of imatinib beginning at weaning suppressed production of cryoglobulin, attenuating both the renal injury … Show more

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Cited by 32 publications
(29 citation statements)
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“…A transgenic mouse model with constitutively active thymic stromal lymphopoietin resulted in cryoglobulin production and renal histologic lesions consistent with membranoproliferative GN caused by cryoglobulinemia. 55 Imatinib treatment in this mouse model reduces the cryocrit, serum levels of all immunoglobulins, mature and immature B cells, systemic manifestations of the disease, and C3 glomerular deposition. To highlight the immunomodulatory role of imatinib, the same thymic stromal lymphopoietin tg mouse model was treated with angiotensinconverting enzyme inhibition or angiotensin-receptor blocker therapy alone and showed no improvement in markers of immunologic activation.…”
Section: Imatinib In Murine Models Of Kidney Diseasementioning
confidence: 80%
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“…A transgenic mouse model with constitutively active thymic stromal lymphopoietin resulted in cryoglobulin production and renal histologic lesions consistent with membranoproliferative GN caused by cryoglobulinemia. 55 Imatinib treatment in this mouse model reduces the cryocrit, serum levels of all immunoglobulins, mature and immature B cells, systemic manifestations of the disease, and C3 glomerular deposition. To highlight the immunomodulatory role of imatinib, the same thymic stromal lymphopoietin tg mouse model was treated with angiotensinconverting enzyme inhibition or angiotensin-receptor blocker therapy alone and showed no improvement in markers of immunologic activation.…”
Section: Imatinib In Murine Models Of Kidney Diseasementioning
confidence: 80%
“…[53][54][55] In the two LN models, imatinib reduced anti-double-stranded DNA levels and decreased immune complex deposition. 53,54 This resulted in improved survival, creatinine, and proteinuria.…”
Section: Imatinib In Murine Models Of Kidney Diseasementioning
confidence: 98%
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“…23 Tyrosine kinases are important therapeutic targets; for example, imatinib, an inhibitor of tyrosine kinase downstream of platelet-derived growth factor receptor, has been shown to reduce the severity of established experimental glomerulonephritis, including NTN, in association with reduction of glomerular IL-1␤ and MCP-1. 18,26 Our results suggested that Syk inhibition has potential in the treatment of patients with glomerulonephritis.…”
mentioning
confidence: 67%
“…As previously described, the liver and lung inflammation was scored semiquantitatively on a scale of 0 to 3: 0, no inflammation; 1, mild; 2, moderate; 3, severe, with regard to the extent and density of leukocytic infiltration. 15,17 All data are expressed as mean Ϯ SEM. Statistical analysis of the data for multiple groups was performed by TSLPtg mice developed typical features of cryoglobulin-associated MPGN as described previously.…”
Section: Analytical Methods and Statistical Analysismentioning
confidence: 99%