Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway
Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the reno...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00851/full |
| _version_ | 1818963426224898048 |
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| author | Wenlin Chen Xiaoqing Xi Shuangyang Zhang Cong Zou Renrui Kuang Zhenfeng Ye Yawei Huang Honglin Hu |
| author_facet | Wenlin Chen Xiaoqing Xi Shuangyang Zhang Cong Zou Renrui Kuang Zhenfeng Ye Yawei Huang Honglin Hu |
| author_sort | Wenlin Chen |
| collection | DOAJ |
| description | Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway. |
| first_indexed | 2024-12-20T12:45:02Z |
| format | Article |
| id | doaj.art-d5ddcf79642a42d5b0680ce47aa42b06 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T12:45:02Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d5ddcf79642a42d5b0680ce47aa42b062022-12-21T19:40:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-08-01910.3389/fphar.2018.00851378761Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy PathwayWenlin Chen0Xiaoqing Xi1Shuangyang Zhang2Cong Zou3Renrui Kuang4Zhenfeng Ye5Yawei Huang6Honglin Hu7Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Hospital of Wuchang, Wuhan, ChinaDepartment of Endocrinology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaRenal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway.https://www.frontiersin.org/article/10.3389/fphar.2018.00851/fullpioglitazonerenal ischemia reperfusion injuryperoxisome proliferators-activated receptor-γautophagycell apoptosis |
| spellingShingle | Wenlin Chen Xiaoqing Xi Shuangyang Zhang Cong Zou Renrui Kuang Zhenfeng Ye Yawei Huang Honglin Hu Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway Frontiers in Pharmacology pioglitazone renal ischemia reperfusion injury peroxisome proliferators-activated receptor-γ autophagy cell apoptosis |
| title | Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway |
| title_full | Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway |
| title_fullStr | Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway |
| title_full_unstemmed | Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway |
| title_short | Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway |
| title_sort | pioglitazone protects against renal ischemia reperfusion injury via the amp activated protein kinase regulated autophagy pathway |
| topic | pioglitazone renal ischemia reperfusion injury peroxisome proliferators-activated receptor-γ autophagy cell apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00851/full |
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