Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation
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 artifici...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/1390418 |
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| author | Chao Wang Xiao-xia Hou Hong-liang Rui Li-jing Li Jing Zhao Min Yang Li-jun Sun Hong-rui Dong Hong Cheng Yi-Pu Chen |
| author_facet | Chao Wang Xiao-xia Hou Hong-liang Rui Li-jing Li Jing Zhao Min Yang Li-jun Sun Hong-rui Dong Hong Cheng Yi-Pu Chen |
| author_sort | Chao Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-68fc7b9eb2a74e288f845979914c3b2e |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-68fc7b9eb2a74e288f845979914c3b2e2025-02-03T01:25:27ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/13904181390418Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome ActivationChao Wang0Xiao-xia Hou1Hong-liang Rui2Li-jing Li3Jing Zhao4Min Yang5Li-jun Sun6Hong-rui Dong7Hong Cheng8Yi-Pu Chen9Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaDivision of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, ChinaBackground/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.http://dx.doi.org/10.1155/2018/1390418 |
| spellingShingle | Chao Wang Xiao-xia Hou Hong-liang Rui Li-jing Li Jing Zhao Min Yang Li-jun Sun Hong-rui Dong Hong Cheng Yi-Pu Chen Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation Journal of Diabetes Research |
| title | Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation |
| title_full | Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation |
| title_fullStr | Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation |
| title_full_unstemmed | Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation |
| title_short | Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation |
| title_sort | artificially cultivated ophiocordyceps sinensis alleviates diabetic nephropathy and its podocyte injury via inhibiting p2x7r expression and nlrp3 inflammasome activation |
| url | http://dx.doi.org/10.1155/2018/1390418 |
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