High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells
While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resul...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/6973175 |
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| author | Hong Feng Junling Gu Fang Gou Wei Huang Chenlin Gao Guo Chen Yang Long Xueqin Zhou Maojun Yang Shuang Liu Shishi Lü Qiaoyan Luo Yong Xu |
| author_facet | Hong Feng Junling Gu Fang Gou Wei Huang Chenlin Gao Guo Chen Yang Long Xueqin Zhou Maojun Yang Shuang Liu Shishi Lü Qiaoyan Luo Yong Xu |
| author_sort | Hong Feng |
| collection | DOAJ |
| description | While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy. |
| format | Article |
| id | doaj-art-be9fc6544db740b8b38c2f6d124c4f1a |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-be9fc6544db740b8b38c2f6d124c4f1a2025-02-03T05:52:14ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/69731756973175High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial CellsHong Feng0Junling Gu1Fang Gou2Wei Huang3Chenlin Gao4Guo Chen5Yang Long6Xueqin Zhou7Maojun Yang8Shuang Liu9Shishi Lü10Qiaoyan Luo11Yong Xu12Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, The Fifth People’s Hospital of Chongqing, Chongqing 400062, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaDepartment of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, ChinaWhile inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.http://dx.doi.org/10.1155/2016/6973175 |
| spellingShingle | Hong Feng Junling Gu Fang Gou Wei Huang Chenlin Gao Guo Chen Yang Long Xueqin Zhou Maojun Yang Shuang Liu Shishi Lü Qiaoyan Luo Yong Xu High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells Journal of Diabetes Research |
| title | High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells |
| title_full | High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells |
| title_fullStr | High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells |
| title_full_unstemmed | High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells |
| title_short | High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells |
| title_sort | high glucose and lipopolysaccharide prime nlrp3 inflammasome via ros txnip pathway in mesangial cells |
| url | http://dx.doi.org/10.1155/2016/6973175 |
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