骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移

王和西; 刘学洋; 柳明; 聂东梓; 张尧

doi:10.16016/j.1000-5404.202104189

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骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移

基础医学 | 更新时间：2026-01-09

- 骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移
- Bone marrow mesenchymal stem cell-derived exosomes promote proliferation, invasion and migration of renal cancer cells by regulating cholestanol metabolism
- 第三军医大学学报 2021年43卷第20期页码：2189-2198
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院泌尿外科
- 作者简介：
  
  [ 张尧，zhangyao07407@126.com ZHANG Yao,E-mail: zhangyao07407@126.com
- 基金信息：
- DOI：10.16016/j.1000-5404.202104189
  中图分类号： Q591.5;R329.2;R737.11
- 收稿：2021-04-28，
  
  修回：2021-05-14，
  
  纸质出版：2021-10-30
- 稿件说明：
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王和西, 刘学洋, 柳明, 等. 骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移[J]. 第三军医大学学报, 2021,43(20):2189-2198.

Hexi WANG, Xueyang LIU, Ming LIU, et al. Bone marrow mesenchymal stem cell-derived exosomes promote proliferation, invasion and migration of renal cancer cells by regulating cholestanol metabolism[J]. Journal of Third Military Medical University, 2021, 43(20): 2189-2198.
王和西, 刘学洋, 柳明, 等. 骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移[J]. 第三军医大学学报, 2021,43(20):2189-2198. DOI： 10.16016/j.1000-5404.202104189.

Hexi WANG, Xueyang LIU, Ming LIU, et al. Bone marrow mesenchymal stem cell-derived exosomes promote proliferation, invasion and migration of renal cancer cells by regulating cholestanol metabolism[J]. Journal of Third Military Medical University, 2021, 43(20): 2189-2198. DOI： 10.16016/j.1000-5404.202104189.

摘要

目的

探讨骨髓间充质干细胞外泌体(bone marrow mesenchymal stem cells

BMSCs-Exos)对肾癌细胞增殖、侵袭和迁移能力的影响，明确骨髓间充质干细胞外泌体对肾癌细胞脂质代谢的影响及分子机制。

方法

通过透射电镜和免疫印迹对提取的骨髓间充质干细胞外泌体进行鉴定，摄取实验验证肾癌细胞对骨髓间充质干细胞外泌体的摄取情况。将肾癌细胞Renca分为对照组(常规培养+PBS)和实验组(小鼠BMSCs-Exos 20 μg/mL处理Renca细胞)，采用CCK-8实验观察两组细胞的增殖能力；Transwell实验观察两组细胞的侵袭和迁移能力。液相色谱质谱联用的脂质组学分析肾癌细胞脂质代谢物差异，采用Western blot和qRT-PCR检测胆固醇代谢途径关键酶的表达。

结果

在骨髓间充质干细胞上清液中成功提取分离骨髓间充质干细胞外泌体，透射电镜下呈典型的“杯口状”囊泡，Western blot检测结果发现外泌体标志性蛋白CD63、CD9高表达，且摄取实验表明骨髓间充质干细胞外泌体可被肾癌细胞摄取。细胞功能实验发现，与对照组比较，骨髓间充质干细胞外泌体处理后肾癌细胞的增殖(

0.05)、侵袭和迁移能力(

0.01)均增加。液相色谱质谱联用脂质组学分析显示，外泌体处理后肾癌细胞中牛磺熊去氧胆酸明显降低(

0.05)，胆固醇升高(

0.05)。骨髓间充质干细胞外泌体可调控HMGCR、CYP7A1、CYP7B1表达以影响肾癌细胞胆固醇代谢，促进肾癌细胞增殖和迁移。

结论

骨髓间充质干细胞外泌体可通过调控肾癌细胞内胆固醇代谢关键酶的表达，影响细胞胆固醇代谢，以调控肾癌的增殖、侵袭和迁移能力。

Abstract

Objective

To explore the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on the proliferation

invasion and migration and lipid metabolism of renal cell carcinoma (RCC) cells

and investigate the possible mechanism.

Methods

Firstly

the exosomes derived from mouse BMSCs were identified by transmission electron microscopy and Western blotting. The exosomes uptake experiment of BMSCs was subsequently used to verify whether the derived exosomes could be absorbed by renal cancer cells. RCC Renca cells were divided into control (PBS) and experiment group (20 μg/mL derived exosomes). The proliferation

invasion and migration were measured by CCK-8 assay and Transwell assay

respectively. Metabolite levels were measured with liquid chromatography-mass spectrometry for the differences between the 2 groups of cells. Finally

Western blotting and real-time PCR (qRT-PCR) were utilized to detect the expression of key enzymes of cholesterol metabolism.

Results

Exosomes were successfully derived from the supernatant of mouse BMSCs. Transmission electron microscopy displayed that the mBMSC-derived exosomes showed typical cup-shaped vesicles. Western blotting showed that the levels of exosome-specific proteins CD63 and CD9 were highly expressed after exosome treatment. And the obtained exosomes could be uptaken by RCC cells. The derived exosome treatment significantly promoted proliferation (

0.05) and invasion and migration (

0.01) in RCC cells. Liquid chromatography-mass spectrometry indicated that the treatment also resulted in decreased level of tauroursodeoxycholic acid (TUDCA) (

0.05) and elevated level of cholesterol (

0.05) in RCC cells. Moreover

the treatment could affect the cholesterol metabolism of RCC cells

via

regulating the expression levels of HMGCR

CYP7A1 and CYP7B1

and thus promote the cell proliferation and invasion and migration.

Conclusion

BMSCs-derived exosomes can affect the cholesterol metabolism by regulating the key enzymes

and thus promote the proliferation

invasion and migration of RCC cells.

关键词

Keywords

references

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