Article: 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.
The American journal of Chinese medicine
2017 Volume 45, Issue 5, Page(s) 1075–1092
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 ... ...
| 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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| MeSH term(s) | Animals ; Cell Communication/drug effects ; Cell Communication/genetics ; Cells, Cultured ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/pathology ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Endothelial Cells/metabolism ; Exome/genetics ; Fibrosis ; Kidney/pathology ; Kidney Glomerulus/cytology ; Mesangial Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Phytotherapy ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/metabolism | |||||
| Chemical Substances | Drugs, Chinese Herbal ; Transforming Growth Factor beta1 ; tongxinluo | |||||
| Language | English | |||||
| Publishing date | 2017 | |||||
| Publishing country | Singapore | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 193085-0 | |||||
| ISSN | 0192-415X ; 0090-2942 | |||||
| ISSN | 0192-415X ; 0090-2942 | |||||
| DOI | 10.1142/S0192415X17500586 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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