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Tongxinluo Inhibits Renal Fibrosis in Diabetic Nephropathy: Involvement of the Suppression of Intercellular Transfer of TGF-[Formula: see text]1-Containing Exosomes from GECs to GMCs.

Authors
  • Wu, Xiao-Ming1
  • Gao, Yan-Bin1
  • Xu, Li-Ping1
  • Zou, Da-Wei1
  • Zhu, Zhi-Yao1
  • Wang, Xiao-Lei1
  • Yao, Wei-Jie1
  • Luo, Liang-Tao1
  • Tong, Yu1
  • Tian, Nian-Xiu1
  • Han, Zhe-Ji1
  • Dang, Wan-Yu2
  • 1 * Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, No. 10, Youanmenwai, Xitoutiao, Fengtai District, Beijing 100069, China. , (China)
  • 2 † Beijing Children's Hospital, Capital Medical University, No. 56, Nanlishilu, Xicheng District, Beijing 100045, China. , (China)
Type
Published Article
Journal
The American journal of Chinese medicine
Publication Date
Jan 01, 2017
Volume
45
Issue
5
Pages
1075–1092
Identifiers
DOI: 10.1142/S0192415X17500586
PMID: 28659030
Source
Medline
Keywords
License
Unknown

Abstract

Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-[Formula: see text]1-containing exosomes to activate GMCs through the TGF-[Formula: see text]1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-[Formula: see text]1-containing exosomes from GECs to GMCs. In this study, we demonstrate that TXL can inhibit the secretion of TGF-[Formula: see text]1-containing exosomes from HG-treated GECs. Furthermore, exosomes produced by HG induced-GECs treated with TXL cannot trigger GMC activation, proliferation and extracellular matrix (ECM) overproduction both in vitro and in vivo. These results suggest that TXL can prevent the transfer of TGF-[Formula: see text]1 from GECs to GMCs via exosomes, which may be one of the mechanisms of TXL in the treatment of DN.

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