Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 14, Issue 11, Pages 1545-1557Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.24032
Keywords
Triptolide; Epithelial-mesenchymal transition; MiR-188-5p; PTEN; Diabetic kidney disease
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Funding
- National Natural Science Foundation of China [81273915, 81470187]
- Natural Science Foundation of Tianjin [15ZXHLSY00460, 14JCZDJC33700]
- Science&Technology Development Fund of Tianjin Education Commission for Higher Education [2017KJ210]
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Triptolide possesses the trait of renal protection. Epithelial-mesenchymal transition (EMT) is closely linked to the pathogenesis of diabetic kidney disease (DKD). MicroRNAs have recently emerged as critical regulators of DKD. However, it is poorly understood whether triptolide alleviates renal EMT by regulating microRNAs in DKD. In this study, we found that triptolide decreased albuminuria, improved the renal structure and reduced renal EMT in rats with DKD. Furthermore, activation of the PI3K/AKT signaling pathway was increased in diabetic rats, which was partly reversed by triptolide. Triptolide also alleviated glucose-induced EMT in HK-2 cells in vitro. PI3K/AKT signaling pathway activation was reduced after triptolide treatment. Moreover, triptolide decreased the increase in miR-188-5p expression stimulated by high glucose levels in HK-2 cells. miR-188-5p inhibited PTEN expression by directly interacting with the PTEN 3'-untranslated region. Additionally, downregulation of miR-188-5p, which imitates the effects of triptolide, attenuated the activation of the PI3K/AKT pathway and HG-induced EMT, whereas miR-188-5p overexpression reversed the effects of triptolide on the PI3K/AKT pathway and EMT. In conclusion, we demonstrated that triptolide ameliorates renal EMT via the PI3K/AKT signaling pathway through the interaction between miR-188-5p and PTEN, indicating that miR-188-5p may be a therapeutic target of triptolide in DKD.
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