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

Autor(es):Mostrar menos -

Rafael da Silva Luiz ^[1] ; Rodolfo Rosseto Rampaso ^[2] ; Alef Aragão Carneiro dos Santos ^[3] ; Marcia Bastos Convento ^[4] ; Dulce Aparecida Barbosa ^[5] ; Cassiane Dezoti da Fonseca ^[6] ; Andréia Silva de Oliveira ^[7] ; Agnaldo Caires ^[8] ; Andrei Furlan ^[9] ; Nestor Schor ^[10] ; Fernanda Teixeira Borges

Afiliação do(s) autor(es):Mostrar menos -

^[1] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[2] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[3] Cruzeiro do Sul University. Institute of Physical Activity and Sport Sciences. Interdisciplinary Program in Health Sciences - Brasil

^[4] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[5] Federal University of São Paulo. Paulista School of Nursing - Brasil

^[6] Federal University of São Paulo. Paulista School of Nursing - Brasil

^[7] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[8] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[9] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

^[10] Federal University of São Paulo. Department of Medicine. Nephrology Division - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 27, 2021-12-03.

Resumo

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. (AU)

• Processo FAPESP: 15/23345-9 - MicroRNAs, vesículas extracelulares e células tronco: papel fisiológico, fisiopatológico e potencialidade terapêutica em doenças renais
• Beneficiário: Mirian Aparecida Boim
• Modalidade de apoio: Auxílio à Pesquisa - Temático