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

Autor: Luiz RDS; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Rampaso RR; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Dos Santos AAC; Interdisciplinary Program in Health Sciences, Institute of Physical Activity and Sport Sciences, Cruzeiro do Sul University, São Paulo, SP, Brazil., Convento MB; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Barbosa DA; Paulista School of Nursing, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., da Fonseca CD; Paulista School of Nursing, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., de Oliveira AS; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Caires A; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Furlan A; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Schor N; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil., Borges FT; Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.; Interdisciplinary Program in Health Sciences, Institute of Physical Activity and Sport Sciences, Cruzeiro do Sul University, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: The journal of venomous animals and toxins including tropical diseases [J Venom Anim Toxins Incl Trop Dis] 2021 Dec 03; Vol. 27, pp. e20200187. Date of Electronic Publication: 2021 Dec 03 (Print Publication: 2021).
DOI: 10.1590/1678-9199-JVATITD-2020-0187
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare that they have no competing interests.
Databáze: MEDLINE