BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model.

IF 1.8 3区 医学 Q4 TOXICOLOGY
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
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引用次数: 0

Abstract

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.

Abstract Image

Abstract Image

Abstract Image

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。
背景:骨髓间充质基质细胞(BM-MSC)及其细胞外囊泡的疗效已被证明可用于广泛的适应症,包括肾脏疾病。然而,通常不考虑骨髓间充质干细胞供体的特征及其潜力。因此,本研究旨在评估经训练的大鼠单侧输尿管梗阻(UUO)模型中BM-MSC分泌的sEV的肾保护能力。方法:利用骨髓间充质干细胞的分化潜力和免疫表型标志物对其进行表征。采用超离心分离sEV,纳米颗粒跟踪分析和western blot对其进行鉴定。通过miR-26a, 126a和296的定量PCR分析检测其miRNA货物。Wistar大鼠接受UUO治疗,同时给予未训练大鼠和训练大鼠BM-MSC分泌的sEV。评估各组肾组织的纤维化介质(转化生长因子β 1和胶原)、cd34血管生成标志物和缺氧诱导因子1α (HIF-1α)。结果:跑步机训练刺激BM-MSC中装载促血管生成miR-296的sEV的产生。与未训练的大鼠相比,用sEVin uuo治疗的大鼠能够减少肾组织中胶原的积累,增加CD34和HIF-1α。在缺氧和暴露于BM-MSC sEV下的管状近端细胞显示HIF-1α和NFR-2(核因子红系2相关因子2)的积累,可能在这些条件下介导对缺氧和氧化应激的反应。结论:与未训练的囊泡相比,训练动物的BM-MSC sEV通过携带296-angiomiR并促进UUO模型的血管生成,显示出更高的肾保护潜力。
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来源期刊
CiteScore
4.80
自引率
8.30%
发文量
39
审稿时长
6-12 weeks
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.
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