PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice
Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the...
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| Format: | Article |
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Wiley
2013-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2013/612971 |
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| author | Ying Sun Zhanjun Jia Gang Liu Li Zhou Mi Liu Baoxue Yang Tianxin Yang |
| author_facet | Ying Sun Zhanjun Jia Gang Liu Li Zhou Mi Liu Baoxue Yang Tianxin Yang |
| author_sort | Ying Sun |
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| description | Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)γ and PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPARγ activation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN. |
| format | Article |
| id | doaj-art-669b7cc1e4d34ab9b8d5b9c03eb2c08d |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
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| series | PPAR Research |
| spelling | doaj-art-669b7cc1e4d34ab9b8d5b9c03eb2c08d2025-02-03T01:00:27ZengWileyPPAR Research1687-47571687-47652013-01-01201310.1155/2013/612971612971PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db MiceYing Sun0Zhanjun Jia1Gang Liu2Li Zhou3Mi Liu4Baoxue Yang5Tianxin Yang6Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USADepartment of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USADepartment of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USADepartment of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USADepartment of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT, USAEvidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)γ and PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPARγ activation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN.http://dx.doi.org/10.1155/2013/612971 |
| spellingShingle | Ying Sun Zhanjun Jia Gang Liu Li Zhou Mi Liu Baoxue Yang Tianxin Yang PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice PPAR Research |
| title | PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice |
| title_full | PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice |
| title_fullStr | PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice |
| title_full_unstemmed | PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice |
| title_short | PPARγ Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice |
| title_sort | pparγ agonist rosiglitazone suppresses renal mpges 1 pge2 pathway in db db mice |
| url | http://dx.doi.org/10.1155/2013/612971 |
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