Department of Anesthesiology, Foshan Women and Children Hospital, Foshan, China.
Zhuhai Campus, Zunyi Medical University, Zhuhai, China.
Ren Fail. 2024 Dec;46(1):2334406. doi: 10.1080/0886022X.2024.2334406. Epub 2024 Apr 4.
A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. , transforming growth factor-β1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts-macrophages communication may provide a novel therapeutic target for kidney fibrosis.
在肾脏纤维化发病机制中，一个关键事件是巨噬细胞向肌成纤维细胞（MMT）的转化。外泌体在肾脏细胞间的串扰和肾纤维化的发展中发挥着重要作用。然而，肌成纤维细胞来源的外泌体在 MMT 过程和肾脏纤维化进展中的作用尚不清楚。在这里，我们研究了肌成纤维细胞来源的外泌体在 MMT 和肾脏纤维化中的作用。转化生长因子-β1 刺激肾脏成纤维细胞向肌成纤维细胞分化，并促进肌成纤维细胞释放外泌体。用外泌体处理 RAW264.7 细胞。我们发现肌成纤维细胞来源的外泌体可触发 MMT。相比之下，用 GW4869 抑制外泌体的产生或耗尽条件培养基中的外泌体，可消除肌成纤维细胞诱导 MMT 的能力。用肌成纤维细胞衍生的外泌体（Myo-Exo）处理的小鼠在叶酸（FA）损伤的肾脏中表现出严重的纤维化病变和更多的 MMT 细胞，而 TANK 结合激酶-1 抑制剂可消除这种作用。此外，抑制外泌体的产生可减少胶原沉积、细胞外基质蛋白积累和 FA 肾病中的 MMT。总之，Myo-Exo 增强了 MMT 和肾脏纤维化。阻断外泌体介导的肌成纤维细胞-巨噬细胞通讯可能为肾脏纤维化提供一个新的治疗靶点。
