PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling
The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome prolifera...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/976089 |
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| author | Koji Hashimoto Yuji Kamijo Takero Nakajima Makoto Harada Makoto Higuchi Takashi Ehara Hidekazu Shigematsu Toshifumi Aoyama |
| author_facet | Koji Hashimoto Yuji Kamijo Takero Nakajima Makoto Harada Makoto Higuchi Takashi Ehara Hidekazu Shigematsu Toshifumi Aoyama |
| author_sort | Koji Hashimoto |
| collection | DOAJ |
| description | The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor α (PPARα), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARα in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARα resulted in high susceptibility to glomerulonephritis. To investigate whether PPARα activation improves the disease activity of MsPGN, we examined the protective effects of a PPARα agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARα, which outweighed the PPARα deterioration associated with the nephritic process. The PPARα activation appeared to suppress the NF-κB signaling pathway in glomeruli by the induction of IκBα, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARα-related medicines against MsPGN. PPARα-related medicines might be useful as a treatment option for CKD. |
| format | Article |
| id | doaj-art-aba1183cb6fa40049eb873227e54a5f4 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-aba1183cb6fa40049eb873227e54a5f42025-02-03T01:09:12ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/976089976089PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB SignalingKoji Hashimoto0Yuji Kamijo1Takero Nakajima2Makoto Harada3Makoto Higuchi4Takashi Ehara5Hidekazu Shigematsu6Toshifumi Aoyama7Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanThe vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor α (PPARα), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARα in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARα resulted in high susceptibility to glomerulonephritis. To investigate whether PPARα activation improves the disease activity of MsPGN, we examined the protective effects of a PPARα agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARα, which outweighed the PPARα deterioration associated with the nephritic process. The PPARα activation appeared to suppress the NF-κB signaling pathway in glomeruli by the induction of IκBα, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARα-related medicines against MsPGN. PPARα-related medicines might be useful as a treatment option for CKD.http://dx.doi.org/10.1155/2012/976089 |
| spellingShingle | Koji Hashimoto Yuji Kamijo Takero Nakajima Makoto Harada Makoto Higuchi Takashi Ehara Hidekazu Shigematsu Toshifumi Aoyama PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling PPAR Research |
| title | PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling |
| title_full | PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling |
| title_fullStr | PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling |
| title_full_unstemmed | PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling |
| title_short | PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling |
| title_sort | pparα activation protects against anti thy1 nephritis by suppressing glomerular nf κb signaling |
| url | http://dx.doi.org/10.1155/2012/976089 |
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