Rafael da Silva Luiz, Rodolfo Rosseto Rampaso, Alef Aragão Carneiro Dos Santos, Marcia Bastos Convento, Dulce Aparecida Barbosa, Cassiane Dezoti da Fonseca, Andréia Silva de Oliveira, Agnaldo Caires, Andrei Furlan, Nestor Schor, Fernanda Teixeira Borges
{"title":"训练动物bm - msc来源的细胞外小泡(sEV)在单侧输尿管梗阻模型中显示出肾保护潜力。","authors":"Rafael da Silva Luiz, Rodolfo Rosseto Rampaso, Alef Aragão Carneiro Dos Santos, Marcia Bastos Convento, Dulce Aparecida Barbosa, Cassiane Dezoti da Fonseca, Andréia Silva de Oliveira, Agnaldo Caires, Andrei Furlan, Nestor Schor, Fernanda Teixeira Borges","doi":"10.1590/1678-9199-JVATITD-2020-0187","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model.</p><p><strong>Methods: </strong>BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α).</p><p><strong>Results: </strong>Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions.</p><p><strong>Conclusion: </strong>The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650265/pdf/","citationCount":"0","resultStr":"{\"title\":\"BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model.\",\"authors\":\"Rafael da Silva Luiz, Rodolfo Rosseto Rampaso, Alef Aragão Carneiro Dos Santos, Marcia Bastos Convento, Dulce Aparecida Barbosa, Cassiane Dezoti da Fonseca, Andréia Silva de Oliveira, Agnaldo Caires, Andrei Furlan, Nestor Schor, Fernanda Teixeira Borges\",\"doi\":\"10.1590/1678-9199-JVATITD-2020-0187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model.</p><p><strong>Methods: </strong>BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α).</p><p><strong>Results: </strong>Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions.</p><p><strong>Conclusion: </strong>The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.</p>\",\"PeriodicalId\":17565,\"journal\":{\"name\":\"Journal of Venomous Animals and Toxins Including Tropical Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2021-12-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650265/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Venomous Animals and Toxins Including Tropical Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/1678-9199-JVATITD-2020-0187\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Venomous Animals and Toxins Including Tropical Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0187","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"TOXICOLOGY","Score":null,"Total":0}
BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model.
Background: The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model.
Methods: BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α).
Results: Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions.
Conclusion: The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.
期刊介绍:
Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD) is a non-commercial academic open access publication dedicated to research on all aspects of toxinology, venomous animals and tropical diseases. Its interdisciplinary content includes original scientific articles covering research on toxins derived from animals, plants and microorganisms. Topics of interest include, but are not limited to:systematics and morphology of venomous animals;physiology, biochemistry, pharmacology and immunology of toxins;epidemiology, clinical aspects and treatment of envenoming by different animals, plants and microorganisms;development and evaluation of antivenoms and toxin-derivative products;epidemiology, clinical aspects and treatment of tropical diseases (caused by virus, bacteria, algae, fungi and parasites) including the neglected tropical diseases (NTDs) defined by the World Health Organization.