Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2
Indoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investi...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/5802973 |
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| author | Shuzhen Li Sijie Cheng Zhenzhen Sun Harr-keshauve Mungun Wei Gong Jing Yu Weiwei Xia Yue Zhang Songming Huang Aihua Zhang Zhanjun Jia |
| author_facet | Shuzhen Li Sijie Cheng Zhenzhen Sun Harr-keshauve Mungun Wei Gong Jing Yu Weiwei Xia Yue Zhang Songming Huang Aihua Zhang Zhanjun Jia |
| author_sort | Shuzhen Li |
| collection | DOAJ |
| description | Indoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investigate the role of IS in modulating mesangial cell (MC) proliferation and the underlying mechanism. The proliferation of MCs induced by IS was determined by cell number counting, DNA synthase rate, and cell cycle phase analysis. COX-2 expression was examined by Western blotting and qRT-PCR, and a specific COX-2 inhibitor NS398 was applied to define its role in IS-induced MC proliferation. Following IS treatment, MCs exhibited increased total cell number, DNA synthesis rate, and number of cells in S and G2 phases paralleled with the upregulation of cyclin A2 and cyclin D1. Next, we found an inducible inflammation-related enzyme COX-2 was remarkably enhanced by IS, and the inhibition of COX-2 by NS398 significantly blocked IS-induced MC proliferation in line with a blockade of PGE2 production. These findings indicated that IS could induce MC proliferation via a COX-2-mediated mechanism, providing new insights into the understanding and therapies of progressive loss of RRF in ESRD. |
| format | Article |
| id | doaj-art-d1240d493e9f484a964f1d354a3f316a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d1240d493e9f484a964f1d354a3f316a2025-02-03T01:12:13ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/58029735802973Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2Shuzhen Li0Sijie Cheng1Zhenzhen Sun2Harr-keshauve Mungun3Wei Gong4Jing Yu5Weiwei Xia6Yue Zhang7Songming Huang8Aihua Zhang9Zhanjun Jia10Department of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing, ChinaIndoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investigate the role of IS in modulating mesangial cell (MC) proliferation and the underlying mechanism. The proliferation of MCs induced by IS was determined by cell number counting, DNA synthase rate, and cell cycle phase analysis. COX-2 expression was examined by Western blotting and qRT-PCR, and a specific COX-2 inhibitor NS398 was applied to define its role in IS-induced MC proliferation. Following IS treatment, MCs exhibited increased total cell number, DNA synthesis rate, and number of cells in S and G2 phases paralleled with the upregulation of cyclin A2 and cyclin D1. Next, we found an inducible inflammation-related enzyme COX-2 was remarkably enhanced by IS, and the inhibition of COX-2 by NS398 significantly blocked IS-induced MC proliferation in line with a blockade of PGE2 production. These findings indicated that IS could induce MC proliferation via a COX-2-mediated mechanism, providing new insights into the understanding and therapies of progressive loss of RRF in ESRD.http://dx.doi.org/10.1155/2016/5802973 |
| spellingShingle | Shuzhen Li Sijie Cheng Zhenzhen Sun Harr-keshauve Mungun Wei Gong Jing Yu Weiwei Xia Yue Zhang Songming Huang Aihua Zhang Zhanjun Jia Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 Mediators of Inflammation |
| title | Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 |
| title_full | Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 |
| title_fullStr | Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 |
| title_full_unstemmed | Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 |
| title_short | Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2 |
| title_sort | indoxyl sulfate induces mesangial cell proliferation via the induction of cox 2 |
| url | http://dx.doi.org/10.1155/2016/5802973 |
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