Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation
Joint Authors
Cheng, Hong
Rui, Hong-liang
Dong, Hong-rui
Sun, Li-Jun
Wang, Chao
Hou, Xiao-xia
Li, Li-jing
Zhao, Jing
Yang, Min
Chen, Yi-Pu
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-11-11
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Background/Aims.
It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS).
Methods.
A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed.
The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined.
The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1β and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively.
Results.
The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages.
ACOS significantly antagonized the above changes.
The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1β, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively.
ACOS also significantly antagonized all the above changes.
Conclusion.
Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.
American Psychological Association (APA)
Wang, Chao& Hou, Xiao-xia& Rui, Hong-liang& Li, Li-jing& Zhao, Jing& Yang, Min…[et al.]. 2018. Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation. Journal of Diabetes Research،Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1183254
Modern Language Association (MLA)
Wang, Chao…[et al.]. Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation. Journal of Diabetes Research No. 2018 (2018), pp.1-16.
https://search.emarefa.net/detail/BIM-1183254
American Medical Association (AMA)
Wang, Chao& Hou, Xiao-xia& Rui, Hong-liang& Li, Li-jing& Zhao, Jing& Yang, Min…[et al.]. Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation. Journal of Diabetes Research. 2018. Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1183254
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1183254