Mild electrical stimulation with heat shock attenuates renal pathology in adriamycin-induced nephrotic syndrome mouse model
| Autor: | Hirofumi Kai, Tatsuya Kondo, Mary Ann Suico, Tsubasa Yokota, Mariam Piruzyan, Keisuke Teramoto, Eiichi Araki, Tsuyoshi Shuto, Kohei Omachi, Yu Tsurekawa, Misato Kamura, Shota Kaseda |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Nephrotic Syndrome animal structures 030232 urology & nephrology lcsh:Medicine Apoptosis Nephritis Hereditary Stimulation Kidney Article Mice 03 medical and health sciences 0302 clinical medicine Focal segmental glomerulosclerosis Edema medicine Albuminuria Animals Phosphorylation Alport syndrome lcsh:Science Protein kinase B Inflammation Mice Inbred BALB C Multidisciplinary Molecular medicine Caspase 3 Glomerulosclerosis Focal Segmental business.industry lcsh:R Glomerulosclerosis medicine.disease Electric Stimulation Disease Models Animal Proteinuria 030104 developmental biology Renal pathology Doxorubicin Creatinine Cancer research Cytokines lcsh:Q medicine.symptom business Nephrotic syndrome Heat-Shock Response Signal Transduction |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-75761-8 |
| Popis: | Nephrotic syndrome (NS) is a renal disorder that is characterized by massive proteinuria, hypoalbuminemia and edema. One of the main causes of NS is focal segmental glomerulosclerosis (FSGS), which has extremely poor prognosis. Although steroids and immunosuppressants are the first line of treatment, some FSGS cases are refractory, prompting the need to find new therapeutic strategies. We have previously demonstrated that an optimized combination treatment of mild electrical stimulation (MES) and heat shock (HS) has several biological benefits including the amelioration of the pathologies of the genetic renal disorder Alport syndrome. Here, we investigated the effect of MES + HS on adriamycin (ADR)-induced NS mouse model. MES + HS suppressed proteinuria and glomerulosclerosis induced by ADR. The expressions of pro-inflammatory cytokines and pro-fibrotic genes were also significantly downregulated by MES + HS. MES + HS decreased the expression level of cleaved caspase-3 and the number of TUNEL-positive cells, indicating that MES + HS exerted anti-apoptotic effect. Moreover, MES + HS activated the Akt signaling and induced the phosphorylation and inhibition of the apoptotic molecule BAD. In in vitro experiment, the Akt inhibitor abolished the MES + HS-induced Akt-BAD signaling and anti-apoptotic effect in ADR-treated cells. Collectively, our study suggested that MES + HS modulates ADR-induced pathologies and has renoprotective effect against ADR-induced NS via regulation of Akt-BAD axis. |
| Databáze: | OpenAIRE |
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