Back to Journals » Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy » Volume 14

PARP-1 and SIRT-1 are Interacted in Diabetic Nephropathy by Activating AMPK/PGC-1α Signaling Pathway

Authors Zhu H, Fang Z, Chen J, Yang Y, Gan J, Luo L, Zhan X

Received 18 November 2020

Accepted for publication 12 January 2021

Published 25 January 2021 Volume 2021:14 Pages 355—366

DOI https://doi.org/10.2147/DMSO.S291314

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Ming-Hui Zou


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 work

Correspondence: Liang Luo
Department of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, People’s Republic of China
Tel/Fax +8613807979503
Email f9461@163.com
Xiaojiang Zhan
Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China
Tel/Fax +8613507919885
Email zhanxiaogang87@163.com

Introduction: 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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]