Effect of Rapamycin on Spleen Size in Longstanding Renal Transplant Recipients

Araújo, Nordeval Cavalcante; Lucena, S.; Rioja, S

doi:10.1016/j.transproceed.2014.03.011

Cited by 9 publications

(10 citation statements)

References 21 publications

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“…A study also reported an increase in the percentage of the liver by 2 weeks administration of RAP in 3 month-old mice [32] , while other study found that liver size and its ratio to body weight were not affected by 1-week administration of RAP in 12-week-old mice [34] . RAP administration significantly decreased the percentage of the spleen to body weight in both genotypes, in agreement with other results showing decreased spleen size by RAP in various experimental conditions [35] , [36] . The percentage of epidydimal fat to body weight increased significantly by RAP in both genotypes.…”

Section: Resultssupporting

confidence: 92%

Rapamycin suppresses postnatal muscle hypertrophy induced by myostatin-inhibition accompanied by transcriptional suppression of the Akt/mTOR pathway

Choi

Yang

Kim

2019

Biochemistry and Biophysics Reports

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Myostatin (MSTN) is a well-known negative growth factor of muscle mass, and studies have shown that MSTN-inhibition would be a potential strategy to treat muscle atrophy seen in various clinical conditions. Recent studies suggest that MSTN-inhibition induces skeletal muscle hypertrophy through up-regulation of the anabolic Akt/mTOR pathway. Therefore, it was hypothesized that the muscle hypertrophy induced by MSTN-inhibition would be suppressed by the administration of rapamycin (RAP), a mTOR suppressor. A MSTN transgenic mouse strain (MSTN-pro), which is characterized by a postnatal hyper-muscularity due to MSTN inhibition through transgenic overexpression of MSTN propeptide, was used in producing experimental animals. Five-week-old male heterozygous MSTN-pro mice and wild-type littermates were administered with 0 or 3 mg/kg body weight of RAP intraperitoneally every other day for 4 weeks. The effects of RAP on muscle growth, mRNA abundance of signaling components of the Akt/mTOR pathway, and myogenic regulatory factors (MyoD, Myf5, MyoG, and Mrf4) were examined in comparison to wild-type mice. Body weight gain of MSTN-pro mice was significantly greater than that of wild-type mice. RAP suppressed body weight gain and muscle mass in both MSTN-pro and wild-type mice. The extent of both body weight and muscle mass suppression was significantly greater in MSTN-pro mice than in wild-type mice. Real-time qPCR analysis showed that mRNA abundance of the signaling molecules of the Akt/mTOR pathway, including Akt, p70S6K, and 4E-BP1, were significantly higher in MSTN-pro mice. RAP treatment decreased mRNA abundance of Akt, p70S6K and 4E-BP1 only in MSTN-pro mice. mRNA abundances of MyoD and MyoG were not affected by MSTN suppression or RAP treatment. mRNA abundance of Myf5 was decreased by RAP, but not affected by MSTN suppression. mRNA abundance of Mrf4 was decreased by MSTN suppression. RAP treatment decreased mRNA abundance of Mrf4 only in wild type mice. Results of this study indicate that transcriptional regulation of signaling components of the Akt/mTOR pathway and myogenic regulatory transcription factor Mrf4 is involved in the enhancement of skeletal muscle mass induced by MSTN suppression.

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Section: Resultssupporting

confidence: 92%

Rapamycin suppresses postnatal muscle hypertrophy induced by myostatin-inhibition accompanied by transcriptional suppression of the Akt/mTOR pathway

Choi

Yang

Kim

2019

Biochemistry and Biophysics Reports

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“…The smaller spleen size in the rapamycin group of our study favors an anti-proliferative effect of rapamycin on microglia within the SN as well. The effect of rapamycin on spleen size reduction has been already reported after kidney transplant [ 61 ] and was reproduced in the present study. Furthermore, mTOR inhibitors significantly reduced tumor volume in tuberous sclerosis [ 62 ].…”

Section: Discussionsupporting

confidence: 84%

Transcranial sonography depicts a larger substantia nigra echogenic area in renal transplant patients on calcineurin inhibitors than on rapamycin

2022

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Background After kidney transplantation neurologic manifestations may develop, including Parkinson’s disease (PD). An enlarged substantia nigra (SN) by transcranial sonography has been recognized as a marker of PD. Methods In renal transplant recipients (RTRs = 95) and controls (n = 20), measurement of mesencephalon, SN, third ventricle, spleen and carotid intima-media thickness (cIMT) and middle cerebral artery (MCA), kidney and spleen arteries Doppler resistive index (RI) were performed. Results RTRs had larger SN, third ventricle and cIMT and higher renal RI than controls. The SN was larger in the CNIs group than in controls and rapamycin group, while the third ventricle was similar between patients but larger than in controls. In RTRs, SN showed a direct linear correlation with spleen and the third ventricle with age, cIMT and RI of the MCA, kidney and spleen. In CNIs group the SN correlated positively with age and cIMT, while the third ventricle reproduced RTRs correlations. Rapamycin group showed a direct linear relationship between the third ventricle and age and RI of the MCA, kidney and spleen; SN showed no correlations. Conclusion RTRs on CNIs present a larger SN area than on rapamycin, probably due to the antiproliferative effect of rapamycin. This finding might be relevant when interpreting TCS in RTRs.

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“…However, given that the reduction of spleen size was associated with improvements in anaemia, it is probably secondary to reduced erythrocyte sickling. There may also be other pathways involved in mTOR inhibition on spleen size as previous studies have shown that sirolimus leads to reduced spleen size in non‐SCD human populations without compromising splenic function (Araujo et al , ). As splenectomy did not improve anaemia in SCD mice, the spleen is unlikely to be the relevant target organ for sirolimus with regards to the improvement of anaemia in SCD.…”

Section: Discussionmentioning

confidence: 99%

mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease

et al. 2016

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Summary Mechanistic target of rapamycin (mTOR) has been shown to play an important role in red blood cell physiology, with inhibition of mTOR signalling leading to alterations in erythropoiesis. To determine if mTOR inhibition would improve anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual mTORC1/2 inhibitor, INK128. 1 week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3 weeks of treatment. Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in SCD mice. Following middle cerebral artery occlusion, stroke size was reduced in SCD mice treated with sirolimus. In conclusion, mTOR inhibition is protective against anaemia and organ damage in a murine model of SCD.

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Effect of Rapamycin on Spleen Size in Longstanding Renal Transplant Recipients

Cited by 9 publications

References 21 publications

Rapamycin suppresses postnatal muscle hypertrophy induced by myostatin-inhibition accompanied by transcriptional suppression of the Akt/mTOR pathway

Rapamycin suppresses postnatal muscle hypertrophy induced by myostatin-inhibition accompanied by transcriptional suppression of the Akt/mTOR pathway

Transcranial sonography depicts a larger substantia nigra echogenic area in renal transplant patients on calcineurin inhibitors than on rapamycin

mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease

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