Low dose of triptolide ameliorates podocyte epithelial-mesenchymal transition induced by high dose of D-glucose via inhibiting Wnt3α/β-catenin signaling pathway activation.
10.19540/j.cnki.cjcmm.20171027.013
- Author:
Ge SHI
1
;
Wei WU
1
;
Yi-Gang WAN
2
;
He Wei-Ming HEX
3
;
Yue TU
4
;
Wen-Bei HAN
1
;
Bu-Hui LIU
1
;
Ying-Lu LIU
1
;
Zi-Yue WAN
5
Author Information
1. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Chinese Medicine and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.
2. Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
3. Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
4. Department of TCM Health Preservation, Second Clinic Medical School, Nanjing University of Chinese Medicine, Nanjing 210023, China.
5. Department of Social Work, Meiji Gakuin University, Tokyo 108-8636, Japan.
- Publication Type:Journal Article
- Keywords:
Wnt3α/β-catenin signaling pathway;
diabetic nephropathy;
epithelial-mesenchymal transition;
podocyte;
triptolide
- MeSH:
Animals;
Cells, Cultured;
Diterpenes;
pharmacology;
Epithelial-Mesenchymal Transition;
Epoxy Compounds;
pharmacology;
Glucose;
Mice;
Phenanthrenes;
pharmacology;
Podocytes;
drug effects;
Wnt Signaling Pathway;
Wnt3A Protein;
metabolism;
beta Catenin;
metabolism
- From:
China Journal of Chinese Materia Medica
2018;43(1):139-146
- CountryChina
- Language:Chinese
-
Abstract:
To explore the effects and molecular mechanisms of triptolide（TP）on improving podocyte epithelial-mesenchymal transition（EMT）induced by high dose of D-glucose（HG）, the immortalized podocytes of mice were divided into the normal group（N）, the high dose of D-glucose group（HG）, the low dose of TP group（L-TP）, the high dose of TP group（H-TP）and the mannitol group（MNT）, and treated by the different measures respectively. More specifically, the podocytes in each group were separately treated by D-glucose（DG, 5 mmol·L⁻¹）or HG（25 mmol·L⁻¹）or HG（25 mmol·L⁻¹）+ TP（3 μg·L⁻¹）or HG（25 mmol·L⁻¹）+ TP（10 μg·L⁻¹）or DG（5 mmol·L⁻¹）+ MNT（24.5 mmol·L⁻¹）. After the intervention for 24, 48 and 72 hours, firstly, the activation of podocyte proliferation was investigated. Secondly, the protein expression levels of the epithelial markers in podocytes such as nephrin and podocin, the mesenchymal markers such as desmin and collagen Ⅰ and the EMT-related mediators such as snail were detected respectively. Finally, the protein expression levels of Wnt3α and β-catenin as the key signaling molecules in Wnt3α/β-catenin pathway were examined severally. The results indicated that, HG could cause the low protein expression levels of nephrin and podocin and the high protein expression levels of desmin, collagen Ⅰ and snail in podocytes, and inducing podocyte EMT. On the other hand, HG could cause the high protein expression levels of Wnt3α and β-catenin in podocytes, and activating Wnt3α/β-catenin signaling pathway. In addition, L-TP had no effect on the activation of podocyte proliferation, the co-treatment of L-TP and HG could significantly recover the protein expression levels of nephrin and podocin, inhibit the protein expression levels of desmin, collagen I and snail in podocytes, thus, further improving podocyte EMT. And that, the co-treatment of L-TP and HG could obviously decrease the high protein expression levels of Wnt3α and β-catenin induced by HG in podocytes, and inhibit Wnt3α/β-catenin signaling pathway activation. On the whole, HG can induce podocyte EMT by activating Wnt3α/β-catenin signaling pathway; L-TP can ameliorate podocyte EMT through inhibiting Wnt3α/β-catenin signaling pathway activation, which may be one of the effects and molecular mechanisms .
