Jianjie Wang, Jianqin Zou, Cheng Zhao, Han Yu, Jiajia Teng, Lei Dong
{"title":"丁香紫杉醇通过HSP90抑制2型心肾综合征的心肾纤维化","authors":"Jianjie Wang, Jianqin Zou, Cheng Zhao, Han Yu, Jiajia Teng, Lei Dong","doi":"10.1177/09603271231165678","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear.</p><p><strong>Methods: </strong>Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 10<sup>11</sup> μg) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-β1 in the myocardium and kidney were measured by immunohistochemistry and western blotting.</p><p><strong>Results: </strong>Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol.</p><p><strong>Conclusions: </strong>Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.</p>","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2.\",\"authors\":\"Jianjie Wang, Jianqin Zou, Cheng Zhao, Han Yu, Jiajia Teng, Lei Dong\",\"doi\":\"10.1177/09603271231165678\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear.</p><p><strong>Methods: </strong>Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 10<sup>11</sup> μg) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-β1 in the myocardium and kidney were measured by immunohistochemistry and western blotting.</p><p><strong>Results: </strong>Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol.</p><p><strong>Conclusions: </strong>Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.</p>\",\"PeriodicalId\":13181,\"journal\":{\"name\":\"Human & Experimental Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human & Experimental Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/09603271231165678\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human & Experimental Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09603271231165678","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2.
Background: Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear.
Methods: Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 1011 μg) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-β1 in the myocardium and kidney were measured by immunohistochemistry and western blotting.
Results: Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol.
Conclusions: Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.
期刊介绍：
Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods
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