Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, China.
School of Pharmacy, Anhui Medical University, Hefei, China.
FASEB J. 2019 Aug;33(8):9279-9290. doi: 10.1096/fj.201802427RRR. Epub 2019 Jun 4.
Diabetes nephropathy (DN) is characterized by abnormal interactions between kidney-infiltrating macrophages and glomerular mesangial cells. Recently, a novel cell-cell communication mediated by exosomes has gained attention. Exosomes are membrane-bound vesicles that contain a variety of molecules such as proteins, lipids, DNA, mRNA, and microRNAs. Exosomes play an important role in the pathogenesis of DN. In this study, we show that high glucose (HG) led to increased excretion of exosomes from macrophages. Mesangial cells took up exosomes , which resulted in the activation and proliferation of mesangial cells and the secretion of extracellular matrix and inflammatory cytokines. In addition, C57BL/6 mice injected with exosomes from HG-treated macrophages showed morphologic and functional changes. We then showed that exosomes from HG-treated TGF-β1 knockdown macrophages induced less extracellular matrix and fewer inflammatory factors in mesangial cells compared with vector control. Our findings suggest that TGF-β1 mRNA in exosomes serves a role between macrophages and mesangial cells by activating the TGF-β1/ mothers against decapentaplegic homolog 3 pathway.-Zhu, Q.-J., Zhu, M., Xu, M.-X., Meng, X.-M., Wu, Y.-G. Exosomes from high glucose-treated macrophages activate glomerular mesangial cells TGF-β1/Smad3 pathway and .
糖尿病肾病（DN）的特征是肾脏浸润的巨噬细胞和肾小球系膜细胞之间异常相互作用。最近，一种新型的细胞间通讯方式——外泌体引起了人们的关注。外泌体是一种膜结合的囊泡，包含多种分子，如蛋白质、脂质、DNA、mRNA 和 microRNAs。外泌体在 DN 的发病机制中起着重要作用。在本研究中，我们表明高糖（HG）导致巨噬细胞分泌的外泌体增加。肾小球系膜细胞摄取外泌体，导致系膜细胞的激活和增殖以及细胞外基质和炎症细胞因子的分泌。此外，用 HG 处理的巨噬细胞来源的外泌体注射的 C57BL/6 小鼠表现出形态和功能改变。然后我们表明，与空载体相比，来自 HG 处理的 TGF-β1 敲低巨噬细胞的外泌体在系膜细胞中诱导的细胞外基质和炎症因子较少。我们的研究结果表明，外泌体中的 TGF-β1 mRNA 通过激活 TGF-β1/Smad3 通路，在巨噬细胞和肾小球系膜细胞之间发挥作用。
