Influence of tacrolimus on podocyte injury inducted by angiotensin II

Yu, Shengyou; Yu, Li; Hao, Zhihong; Ma, Yuan-Yuan

doi:10.1177/1470320314568520

Cited by 9 publications

(6 citation statements)

References 21 publications

(20 reference statements)

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“…To determine whether CsA and FK506 alleviate podocyte injury by reducing mitochondria dependent apoptosis, we preincubated PAN-treated podocytes with CsA or FK506 in vitro . Our results, consistent with previous findings142732, reported the anti-apoptotic effects of FK506 on podocytes. However, the effects of CsA on podocyte apoptosis are controversial.…”

Section: Discussionsupporting

confidence: 94%

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

Shen

Jiang

Ying

et al. 2016

Sci Rep

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Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 94%

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

Shen

Jiang

Ying

et al. 2016

Sci Rep

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“…9 Researchers suggested that TAC inhibited podocyte apoptosis through lowering TRPC6 expression. 21 Cabin1 is a natural selective inhibitor of CN, targeted inhibition of CN by Cabin1 prevented cardiomyocyte hypertrophy 22 and regulated the synaptic endocytosis of neurotransmitter vesicles. 23 Furthermore, researchers demonstrated that overexpression of Cabin1 in rheumatoid arthritis mice induced fibroblast-like synoviocytes apoptosis and alleviated arthritis.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus restores podocyte injury and stabilizes the expression of Cabin1 in 5/6 nephrectomized rats

et al. 2016

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Podocyte injury is a vital factor, which induces massive proteinuria. Studies have shown that tacrolimus (TAC) protected podocyte via stabilizing cytoskeleton. Our latest study indicates that calcineurin binding protein 1 (Cabin1) undergoes nuclear translocation during podocytes injury. Whether TAC targets on Cabin1 during podocyte injury is still not clear. This study establishes non-immunological proteinuric model. To observe the effect of the treatment of TAC on Cabin1 expression in 5/6 nephrectomized rats. Sprague-Dawley rats were injected with TAC (0.2 mg/kg/day) for 4-8 weeks after 5/6 nephrectomy. Then, rats were sacrificed in the eighth week after operation, renal tissues were processed for morphological studies under light and electrical microscope. Cabin1 expression and distribution were detected by western blot and indirect immunofluorescence staining. In 5/6 nephrectomized rats, urinary protein excretion reached 90.2 ± 30.1 mg/24 h, glomerular sclerosis index and tubulointerstitial fibrosis score were significantly increased, and widespread of podocyte foot processes fusion was found. Moreover, Cabin1 protein expression was markedly increased, and its distribution became much more obviously in podocytes nuclei. In TAC treated rats, urinary protein excretion significantly decreased (44.9 ± 22.5 mg/24 h), glomerular sclerosis and tubulointerstitial fibrosis were alleviated, and podocyte foot processes fusion was inhibited. Furthermore, TAC alleviated the increased protein expression and abnormal distribution of Cabin1. In conclusion, TAC restores podocyte injury and stabilizes the expression of Cabin1. Cabin1 may become a new target to demonstrate the mechanism of TAC in podocyte injury.

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“…TAC effectively inhibits TRPC6 overexpression. Therefore, TAC reduces podocyte apoptosis and inhibits the damaging effects of angiotensin II on podocytes (23). Peng et al showed that TAC treatment reduces glomerular angiopoietin-like 4, glomerular immune deposits, and circulating IgG levels; decreases existing proteinuria; and promotes podocyte repair (24).…”

Section: Discussionmentioning

confidence: 99%

Comparison of tacrolimus with or without prednisone therapy in primary membranous nephropathy : A retrospective clinical study

Zhang,

Dou,

Gao

et al. 2023

Preprint

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Objective: Previous studies have shown tacrolimus monotherapy and dual therapy with tacrolimus and low-dose prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. We compared the safety and efficacy and relapse rates of following these treatment regimens in primary membranous nephropathy in this study. Methods: One hundred and thirty-two patients(a total of 302 patients were excluded) diagnosed with MN viarenal needle biopsy at the First Affiliated Hospital of Zhengzhou University between January 2015 and June 2019 were retrospectively analyzed. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T+P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. High titer (PLA2Rab>150 RU / ml) may affect the outcome of PMN patients and therefore may be confounding factors, we performed a subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. Nineteen patients had a high titer in the T + P group, and 21 patients in the T group had a high titer. Patients were treated for approximately 48 weeks; observations were noted. Results: The T group had a remission rate of 64.62%, while the T + P group had a remission rate of 88.06%; the mean remission times were 21.82±2.66 weeks and 10.80±1.91 weeks, respectively. The relapse rate for the T group was 23.08%, and that for the T + P group was 4.48%. The PLA2Rab levels and 24-hour urine proteinuria levels were significantly different between the two groups.There were no significant differences in serum creatinine levels or glomerular filtration rates between the groups. In addition, the groups had no significant differences in complications, including infection, gastrointestinal syndrome, hepatic dysfunction, hyperglycemia, osteoporosis, and new-onset hypertension. Conclusions: Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.

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Influence of tacrolimus on podocyte injury inducted by angiotensin II

Cited by 9 publications

References 21 publications

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

Tacrolimus restores podocyte injury and stabilizes the expression of Cabin1 in 5/6 nephrectomized rats

Comparison of tacrolimus with or without prednisone therapy in primary membranous nephropathy : A retrospective clinical study

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