Department of Urology, The Third Affiliated Hospital of Soochow University, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
Tissue Eng Part A. 2022 Jul;28(13-14):651-659. doi: 10.1089/ten.TEA.2021.0190. Epub 2022 May 19.
Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-β1 (TGF-β1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-β1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF. Impact statement Renal fibrosis (RF) is an important pathological change in chronic kidney disease that ultimately leads to end-stage renal failure, and effective treatments remain elusive. In this study, there are two contributions. First, our results suggest that bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exs) can prevent transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells through Nedd4L trafficking, which activates autophagy. Second, the improvement effects of BM-MSC-Ex on TGF-β1-induced HK-2 EMT can be enhanced by ceria nanoparticles (CeNPs). The findings in this study may be extended to RF: BM-MSC-Exs may be used as a novel treatment to improve RF.
肾纤维化 (RF) 使患者面临慢性肾脏病进展的风险增加，而有效的治疗方法仍难以捉摸。间充质干细胞 (MSC) 衍生的外泌体被认为是治疗组织损伤的一种新方法。我们的研究旨在探讨骨髓 MSC 衍生的外泌体 (BM-MSC-Ex) 对转化生长因子-β1 (TGF-β1) 诱导的肾小管上皮细胞 (HK-2 细胞) 纤维化的影响及其相关机制。在这里，我们发现 BM-MSC-Ex 可以抑制 TGF-β1 诱导的 HK-2 细胞上皮-间充质转化 (EMT)，并且可能涉及 BM-MSC-Ex 的自噬激活。此外，我们首次报道，在氧化铈纳米颗粒 (CeNPs) 处理后，通过上调 MSC 的 Nedd4L 表达和促进包含 Nedd4L 的外泌体分泌，BM-MSC-Ex 对 EMT 的改善作用明显增强。此外，Nedd4L 可以激活 HK-2 细胞中的自噬。总之，BM-MSC-Ex 通过转运 Nedd4L 防止 TGF-β1 诱导的肾小管上皮细胞 EMT，从而激活自噬。该实验结果可能扩展到 RF，通过 BM-MSC-Ex 也可用于改善 RF 的新型治疗。
