Division of Nephrology and National Clinical, Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu 610041, P. R. China.
Department of Nephrology, Lanzhou University Second Hospital, Lanzhou 730030, P. R. China.
Am J Chin Med. 2020;48(7):1715-1729. doi: 10.1142/S0192415X20500858. Epub 2020 Nov 5.
Pterostilbene (PTB) is a derivative of resveratrol present in grapes and blueberries. PTB is structurally similar to resveratrol, possessing properties such as being analgesic, anti-aging, antidiabetic, anti-inflammatory, anti-obesity, anti-oxidation, cholesterol-reductive, and neuroprotective. However, there have not been reports on the effect of PTB on macrophage-myofibroblast transition (MMT) induced fibrosis in kidney. In this study, we investigated the antifibrotic effects of PTB on the mouse unilateral ureteral obstruction (UUO) model and MMT cells. Kidneys subjected to UUO with PTB treatment were collected for the investigation of PTB mediating MMT derived renal interstitial fibrosis. We conducted kidney RNA-seq transcriptomes and TGF-[Formula: see text]1-induced bone marrow-derived macrophages assays to determine the mechanisms of PTB. We found that PTB treatment suppressed the interstitial fibrosis in UUO mice. PTB also attenuated the number of MMT cells and . The transcriptomic analysis showed that CXCL10 may play a central role in the process of PTB-treated renal fibrosis. The siRNA-mediated CXCL10 knockdown decreased the number of MMT cells in TGF-[Formula: see text]1-induced bone marrow-derived macrophages. Our results suggested that PTB attenuated renal interstitial fibrosis by mediating MMT by regulating transcriptional activity of CXCL10.
紫檀芪(PTB)是一种存在于葡萄和蓝莓中的白藜芦醇衍生物。PTB 结构上与白藜芦醇相似,具有镇痛、抗衰老、抗糖尿病、抗炎、抗肥胖、抗氧化、降胆固醇和神经保护等特性。然而,目前尚无关于 PTB 对肾脏中巨噬细胞-肌成纤维细胞转化(MMT)诱导纤维化影响的报道。在这项研究中,我们研究了 PTB 对单侧输尿管梗阻(UUO)模型和 MMT 细胞的抗纤维化作用。收集接受 UUO 治疗并用 PTB 处理的肾脏,以研究 PTB 介导的 MMT 引起的肾间质纤维化。我们进行了肾脏 RNA-seq 转录组和 TGF-β1 诱导的骨髓来源巨噬细胞检测,以确定 PTB 的作用机制。结果发现,PTB 治疗抑制了 UUO 小鼠的间质纤维化。PTB 还减少了 MMT 细胞的数量和 。转录组分析表明,CXCL10 可能在 PTB 处理的肾纤维化过程中发挥核心作用。siRNA 介导的 CXCL10 敲低减少了 TGF-β1 诱导的骨髓来源巨噬细胞中的 MMT 细胞数量。我们的结果表明,PTB 通过调节 CXCL10 的转录活性来介导 MMT 从而减轻肾间质纤维化。