Triptolide inhibits NLRP3 inflammasome activation and ameliorates podocyte epithelial-mesenchymal transition induced by high glucose.
10.19540/j.cnki.cjcmm.20191114.401
- Author:
Wei WU
1
;
Bu-Hui LIU
2
;
Yi-Gang WAN
1
;
Wei SUN
3
;
Ying-Lu LIU
4
;
Wen-Wen WANG
4
;
Qi-Jun FANG
4
;
Yue TU
5
;
Hong-Yun YEE
4
;
Can-Can YUAN
4
;
Zi-Yue WAN
6
Author Information
1. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School Nanjing 210008,China.
2. 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 Department of Nephrology,the Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029,China.
3. Department of Nephrology,the Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029,China.
4. 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.
5. Department of Traditional Chinese Medicine Health Preservation,Acupuncture,Moxibustion and Massage College, Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine Nanjing 210023,China.
6. Department of Social Work,Meiji Gakuin University Tokyo 108-8636,Japan.
- Publication Type:Journal Article
- Keywords:
NLRP3 inflammasome activation;
diabetic nephropathy;
epithelial-mesenchymal transition;
podocyte;
triptolide
- MeSH:
Animals;
Caspase 1/metabolism*;
Cells, Cultured;
Diabetic Nephropathies;
Diterpenes/pharmacology*;
Epithelial-Mesenchymal Transition;
Epoxy Compounds/pharmacology*;
Glucose;
Inflammasomes/metabolism*;
Interleukin-18/metabolism*;
Interleukin-1beta/metabolism*;
Mice;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Phenanthrenes/pharmacology*;
Podocytes/drug effects*
- From:
China Journal of Chinese Materia Medica
2019;44(24):5457-5464
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this paper was to explore the effects of triptolide( TP),the effective component of Tripterygium wilfordii on improving podocyte epithelial-mesenchymal transition( EMT) induced by high glucose( HG),based on the regulative mechanisms of Nod-like receptor protein 3( NLRP 3) inflammasome in the kidney of diabetic kidney disease( DKD). The immortalized podocytes of mice in vitro were divided into the normal( N) group,the HG( HG) group,the low dose of TP( L-TP) group,the high dose of TP( HTP) group and the mannitol( MNT) group,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( 30 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) + TP( 5 μg·L~(-1))or HG( 30 mmol·L~(-1)) + TP( 10 μg·L~(-1)) or DG( 5 mmol·L~(-1)) + MNT( 24. 5 mmol·L~(-1)). After the treatment of HG or TP at 24,48 and 72 h,firstly,the activation of podocyte proliferation was investigated. Secondly,the protein expression levels of the epithelial markers in podocytes such as nephrin and ZO-1,the mesenchymal markers such as collagen Ⅰ and fibronectin( FN) were detected,respectively. Finally,the protein expression levels of NLRP3 and apoptosis-associated speck-like protein( ASC) as the key signaling molecules of NLRP3 inflammasome activation,as well as the downstream effector proteins including caspase-1,interleutin( IL)-1β and IL-18 were examined,severally. The results indicated that,for the cultured podocytes in vitro,HG could cause the low protein expression levels of nephrin and ZO-1,induce the high protein expression levels of collagen Ⅰ and FN and trigger podocyte EMT. Also HG could cause the high protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 and induce NLRP3 inflammasome activation. On the other hand,the co-treatment of TP( L-TP or H-TP) and HG for podocytes could recover the protein expression levels of nephrin and ZO-1,inhibit the protein expression levels of collagen Ⅰ and FN and ameliorate podocyte EMT. Also the co-treatment of TP( L-TP or H-TP) and HG could down-regulate the protein expression levels of NLRP3 and ASC,inhibit NLRP3 inflammasome activation and reduce the protein expression levels of the downstream effector molecules including caspase-1,IL-1β and IL-18. On the whole,HG could activate NLRP3 inflammasome and induce podocyte EMT in vitro. TP at the appropriate dose range could inhibit NLRP3 inflammasome activation and ameliorate podocyte EMT,which may be one of the critical molecular mechanisms of TP protecting againstpodocyte inflammatory injury in DKD.
