{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:25:33Z","timestamp":1790825133767,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T00:00:00Z","timestamp":1482364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"MEXT KAKENHI \"Ministry of Education, Culture, Sports, Science and Technology\", a Grant-in-Aid for Scientific Research in Japan","award":["25461618"],"award-info":[{"award-number":["25461618"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B\u2010lymphocyte independent adriamycin\u2010induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B\u2010lymphocyte independent mechanism underlying its anti\u2010proteinuric effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adriamycin\u2010induced nephropathy was established in Wistar rats by intravenously injecting 10\u2009mg\/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid\u2010like 3b protein, and podocyte\u2010related proteins were examined using immunofluorescence staining and a reverse transcription\u2010polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rituximab treatment of rats with adriamycin\u2010induced nephropathy significantly reduced urinary protein excretion 14 to 28\u2009days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double\u2010immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid\u2010like 3b. Moreover, sphingomyelin phosphodiesterase, acid\u2010like 3b expression was significantly decreased on day 28 of adriamycin\u2010induced nephropathy, which was also prevented by rituximab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin\u2010induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid\u2010like 3b\u2010dependent mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.12737","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T08:31:29Z","timestamp":1454401889000},"page":"49-57","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Rituximab protects podocytes and exerts anti\u2010proteinuric effects in rat adriamycin\u2010induced nephropathy independent of B\u2010lymphocytes"],"prefix":"10.1111","volume":"22","author":[{"given":"Yuichi","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Niigata University Medical and Dental Hospital  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Ikezumi","sequence":"additional","affiliation":[{"name":"Department of 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