Functional Interaction of the Immunosuppressant Mizoribine with the 14-3-3 Protein

Takahashi, Shuntaro; Wakui, Hideki; Gustafsson, Jan‐Åke; Zilliacus, Johanna; Itoh, Hideaki

doi:10.1006/bbrc.2000.3104

Cited by 95 publications

(66 citation statements)

References 25 publications

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“…It is recognized that the administration of MZR combined with 14-3-3 protein and HSP60 enhances the transcriptional activity of glucocorticoid receptors and thus the effect of steroids (8). It has also been reported that MZR inhibits the action of α3β1 integrin and decreases the motility of fibroblast-specific protein-1-positive fibroblasts, both of which are involved in the progression of interstitial fibrosis in patients with IgAN (9).…”

Section: Discussionmentioning

confidence: 99%

IgA Nephropathy and Psoriatic Arthritis that Improved with Steroid Pulse Therapy and Mizoribine in Combination with Treatment for Chronic Tonsillitis and Epipharyngitis

et al. 2015

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A 65-year-old man was admitted to our hospital with edema and renal dysfunction. He had received a diagnosis of psoriatic arthritis at 50 years of age. As a renal biopsy showed IgA nephropathy (IgAN), bilateral tonsillectomy was performed, and one course of steroid pulse therapy with an oral steroid and mizoribine were subsequently administered. The patient's proteinuria gradually reduced in association with an improvement in the renal function. In addition, the rash and arthralgia were ameliorated. In this case, adding treatment for chronic epipharyngitis accelerated the curative effects, and focal infection therapy consisting of immunosuppressive drugs was effective for both IgAN and psoriatic arthritis.

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Section: Discussionmentioning

confidence: 99%

IgA Nephropathy and Psoriatic Arthritis that Improved with Steroid Pulse Therapy and Mizoribine in Combination with Treatment for Chronic Tonsillitis and Epipharyngitis

et al. 2015

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“…We selected oral PSL 30mg (0.5mg/kg) daily and after 2 month we added MZR for the purpose of tapering the dose of PSL in earlier. It has also been reported that interaction between 14-3-3 proteins, known as MZR-binding protein and glucocorticoid receptors, may enhance the transcriptional activity of the receptor, thus suggesting a steroid-sparing effect of MZR [11]. Taking account of her general condition, we concerned about the recurrence of heart failure during the steroid tapering.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine

Akazawa

Ichinose

Origuchi

et al. 2010

Modern Rheumatology

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“…In addition to its effects on lymphocyte proliferation, mizoribine also stimulates transcriptional activation by the glucocorticoid receptor (GR). 42 It is well known that GR interacts with 14-3-3 proteins, which are a family of conserved regulatory molecules expressed in all eukaryotic cells, and their interaction enhances the transcriptional activity of GR. 43 Takahashi et al demonstrated that mizoribine affected the 14-3-3 protein conformation and dose-dependently enhanced the interaction between GR and 14-3-3 proteins in vitro.…”

Section: Patient Nomentioning

confidence: 99%

“…43 Takahashi et al demonstrated that mizoribine affected the 14-3-3 protein conformation and dose-dependently enhanced the interaction between GR and 14-3-3 proteins in vitro. 42 Therefore, mizoribine directly or indirectly augments GR functional activity via the 14-3-3 proteins. These unique mechanisms may account for the efficacy of mizoribine and prednisone combination therapy, but they do not explain why mizoribine should be administered prior to glucocorticoids.…”

Section: Patient Nomentioning

confidence: 99%

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

Matsumoto¹,

Shimada²,

Nojima³

et al. 2013

Renal Failure

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Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria, Renal Failure, 35:7,[936][937][938][939][940][941] Background: Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Method: Thirteen patients with IMN and nephroticrange proteinuria received combined treatment. Mizoribine was initiated at a dose of 150 mg/ day, and 2-3 months later, 20 mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary proteinto-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Results: Before treatment, patient urinary P/C ranged from 3.7 to 15.9 g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. Conclusion: The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.

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Functional Interaction of the Immunosuppressant Mizoribine with the 14-3-3 Protein

Cited by 95 publications

References 25 publications

IgA Nephropathy and Psoriatic Arthritis that Improved with Steroid Pulse Therapy and Mizoribine in Combination with Treatment for Chronic Tonsillitis and Epipharyngitis

IgA Nephropathy and Psoriatic Arthritis that Improved with Steroid Pulse Therapy and Mizoribine in Combination with Treatment for Chronic Tonsillitis and Epipharyngitis

Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine

Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria

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