PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway
Hengmei Zhu,1,2,* Zhi Fang,3,* Jiehui Chen,2 Yun Yang,2 Jiacheng Gan,4 Liang Luo,5 Xiaojiang Zhan1 1Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Nephrology, Huazhong University of Science and Tec...
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Dove Medical Press
2021
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oai:doaj.org-article:b2f2699e2e3f468daa9a656bbdcdf0902021-12-02T13:53:35ZPARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway1178-7007https://doaj.org/article/b2f2699e2e3f468daa9a656bbdcdf0902021-01-01T00:00:00Zhttps://www.dovepress.com/parp-1-and-sirt-1-are-interacted-in-diabetic-nephropathy-by-activating-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Hengmei Zhu,1,2,* Zhi Fang,3,* Jiehui Chen,2 Yun Yang,2 Jiacheng Gan,4 Liang Luo,5 Xiaojiang Zhan1 1Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Nephrology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 4Department of Nuclear Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, People’s Republic of China; 5Department of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang LuoDepartment of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, People’s Republic of ChinaTel/Fax +8613807979503Email f9461@163.comXiaojiang ZhanDepartment of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaTel/Fax +8613507919885Email zhanxiaogang87@163.comIntroduction: Diabetic nephropathy (DN) is a metabolic disorder characterized by the accumulation of extracellular matrix (ECM). This study aims to investigate whether exists an interplay between poly (ADP-ribose) polymerase 1 (PARP-1) and sirtuin 1 (SIRT-1) in DN via AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) signaling pathway.Methods: Eight-week-old male obese leptin-resistant (db/db) mice and nondiabetic control male C57BLKs/J (db/m) mice were used in this study. Body weight and blood glucose were evaluated after 6 h of fasting, which continues for 4 weeks. The kidney tissues were dissected for Western blot, immunofluorescence (IF) assay. Besides, PARP activity assay, MTT assay, NAD+ qualification, Western blot and IF were also performed to detect the level and relation of PARP-1 and SIRT-1 in mouse mesangial cells (MCs) with or without high glucose followed by inhibiting or elevating PARP-1 and SIRT-1, respectively.Results: Western blotting shows PARP-1 and ECM marker fibronectin (FN) are upregulated while SIRT-1 is downregulated in db/db mice (p< 0.05) or in mouse MCs with high glucose (p< 0.05), which are significantly restored by PARP-1 inhibitor (PJ34) (p< 0.05) and SIRT-1 lentiviral transfected treatment (p< 0.05), or worsened by SIRT-1 inhibitor EX527 (p< 0.05). PJ34 treatment (p < 0.05) or SIRT-1 overexpression (p < 0.05) could increase PGC-1α and p-AMPK levels, concomitant with down expression of FN, however, were reversed in the presence of EX527 (p< 0.05).Discussion: Our results suggest an important relationship between PARP-1 and SIRT-1 through AMPK-PGC-1α pathway, indicating a potential therapeutic method for DN.Keywords: PARP-1, SIRT-1, diabetic nephropathy, AMPK/PGC-1α signaling pathwayZhu HFang ZChen JYang YGan JLuo LZhan XDove Medical Pressarticleparp-1sirt-1diabetic nephropathyampk/pgc-1α signaling pathwaySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 355-366 (2021) |
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parp-1 sirt-1 diabetic nephropathy ampk/pgc-1α signaling pathway Specialties of internal medicine RC581-951 |
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parp-1 sirt-1 diabetic nephropathy ampk/pgc-1α signaling pathway Specialties of internal medicine RC581-951 Zhu H Fang Z Chen J Yang Y Gan J Luo L Zhan X PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| description |
Hengmei Zhu,1,2,* Zhi Fang,3,* Jiehui Chen,2 Yun Yang,2 Jiacheng Gan,4 Liang Luo,5 Xiaojiang Zhan1 1Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Nephrology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 4Department of Nuclear Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, People’s Republic of China; 5Department of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang LuoDepartment of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, People’s Republic of ChinaTel/Fax +8613807979503Email f9461@163.comXiaojiang ZhanDepartment of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaTel/Fax +8613507919885Email zhanxiaogang87@163.comIntroduction: Diabetic nephropathy (DN) is a metabolic disorder characterized by the accumulation of extracellular matrix (ECM). This study aims to investigate whether exists an interplay between poly (ADP-ribose) polymerase 1 (PARP-1) and sirtuin 1 (SIRT-1) in DN via AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) signaling pathway.Methods: Eight-week-old male obese leptin-resistant (db/db) mice and nondiabetic control male C57BLKs/J (db/m) mice were used in this study. Body weight and blood glucose were evaluated after 6 h of fasting, which continues for 4 weeks. The kidney tissues were dissected for Western blot, immunofluorescence (IF) assay. Besides, PARP activity assay, MTT assay, NAD+ qualification, Western blot and IF were also performed to detect the level and relation of PARP-1 and SIRT-1 in mouse mesangial cells (MCs) with or without high glucose followed by inhibiting or elevating PARP-1 and SIRT-1, respectively.Results: Western blotting shows PARP-1 and ECM marker fibronectin (FN) are upregulated while SIRT-1 is downregulated in db/db mice (p< 0.05) or in mouse MCs with high glucose (p< 0.05), which are significantly restored by PARP-1 inhibitor (PJ34) (p< 0.05) and SIRT-1 lentiviral transfected treatment (p< 0.05), or worsened by SIRT-1 inhibitor EX527 (p< 0.05). PJ34 treatment (p < 0.05) or SIRT-1 overexpression (p < 0.05) could increase PGC-1α and p-AMPK levels, concomitant with down expression of FN, however, were reversed in the presence of EX527 (p< 0.05).Discussion: Our results suggest an important relationship between PARP-1 and SIRT-1 through AMPK-PGC-1α pathway, indicating a potential therapeutic method for DN.Keywords: PARP-1, SIRT-1, diabetic nephropathy, AMPK/PGC-1α signaling pathway |
| format |
article |
| author |
Zhu H Fang Z Chen J Yang Y Gan J Luo L Zhan X |
| author_facet |
Zhu H Fang Z Chen J Yang Y Gan J Luo L Zhan X |
| author_sort |
Zhu H |
| title |
PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| title_short |
PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| title_full |
PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| title_fullStr |
PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| title_full_unstemmed |
PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway |
| title_sort |
parp-1 and sirt-1 are interacted in diabetic nephropathy by activating ampk/pgc-1α signaling pathway |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/b2f2699e2e3f468daa9a656bbdcdf090 |
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