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间充质基质细胞同种异体移植的肾保护作用通过ω3刺激PPAR-γ的上调而增强。

The Nephroprotective Effects of the Allogeneic Transplantation with Mesenchymal Stromal Cells Were Potentiated by ω3 Stimulating Up-Regulation of the PPAR-γ.

作者信息

de Oliveira Andreia Silva, Convento Márcia Bastos, Razvickas Clara Versolato, Castino Bianca, Leme Ala Moana, da Silva Luiz Rafael, da Silva Wesley Henrique, da Glória Maria Aparecida, Guirão Tatiana Pinotti, Bondan Eduardo, Schor Nestor, Borges Fernanda Teixeira

机构信息

Translational Medicine Division, Department of Medicine, Federal University of Sao Paulo, São Paulo 04038-901, Brazil.

Nephrology Division, Department of Medicine, Federal University of Sao Paulo, São Paulo 04038-901, Brazil.

出版信息

Pharmaceuticals (Basel). 2023 Oct 18;16(10):1484. doi: 10.3390/ph16101484.

DOI:10.3390/ph16101484
PMID:37895955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10610511/
Abstract

Mesenchymal stromal cells (MSCs) obtained from bone marrow are a promising tool for regenerative medicine, including kidney diseases. A step forward in MSCs studies is cellular conditioning through specific minerals and vitamins. The Omega-3 fatty acids (ω3) are essential in regulating MSCs self-renewal, cell cycle, and survival. The ω3 could act as a ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ). This study aimed to demonstrate that ω3 supplementation in rats could lead to the up-regulation of PPAR-γ in the MSCs. The next step was to compare the effects of these MSCs through allogeneic transplantation in rats subjected to unilateral ureteral obstruction (UUO). Independent of ω3 supplementation in the diet of the rats, the MSCs in vitro conserved differentiation capability and phenotypic characteristics. Nevertheless, MSCs obtained from the rats supplemented with ω3 stimulated an increase in the expression of PPAR-γ. After allogeneic transplantation in rats subjected to UUO, the ω3 supplementation in the rats enhanced some nephroprotective effects of the MSCs through a higher expression of antioxidant enzyme (SOD-1), anti-inflammatory marker (IL-10), and lower expression of the inflammatory marker (IL-6), and proteinuria.

摘要

从骨髓中获取的间充质基质细胞（MSCs）是再生医学（包括肾脏疾病治疗）中一种很有前景的工具。MSCs研究的一个进展是通过特定矿物质和维生素进行细胞预处理。ω-3脂肪酸（ω3）在调节MSCs的自我更新、细胞周期和存活方面至关重要。ω3可作为过氧化物酶体增殖物激活受体γ（PPAR-γ）的配体。本研究旨在证明给大鼠补充ω3可导致MSCs中PPAR-γ的上调。下一步是通过同种异体移植，比较这些MSCs对单侧输尿管梗阻（UUO）大鼠的影响。无论大鼠饮食中是否补充ω3，体外培养的MSCs均保留分化能力和表型特征。然而，从补充了ω3的大鼠中获得的MSCs刺激了PPAR-γ表达的增加。在对UUO大鼠进行同种异体移植后，大鼠补充ω3通过更高水平的抗氧化酶（SOD-1）、抗炎标志物（IL-10）表达以及更低水平的炎症标志物（IL-6）表达和蛋白尿，增强了MSCs的一些肾脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/ff9f60b4dc53/pharmaceuticals-16-01484-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/6261e6a1991a/pharmaceuticals-16-01484-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/ff9f60b4dc53/pharmaceuticals-16-01484-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/6261e6a1991a/pharmaceuticals-16-01484-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/d56b248a7861/pharmaceuticals-16-01484-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/fd77f11e5c90/pharmaceuticals-16-01484-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/4815d6ac34c9/pharmaceuticals-16-01484-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4316/10610511/ff9f60b4dc53/pharmaceuticals-16-01484-g005.jpg

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Front Pharmacol. 2022 Oct 21;13:991059. doi: 10.3389/fphar.2022.991059. eCollection 2022.
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IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension.IL-10 部分介导了 MSC 衍生的细胞外囊泡减轻实验性代谢性肾血管性高血压心肌损伤的能力。
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The Role of Peroxisome Proliferator-Activated Receptors in Kidney Diseases.
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