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Citations to this article

p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease
Zhengwei Ma, … , Changlin Mei, Zheng Dong
Zhengwei Ma, … , Changlin Mei, Zheng Dong
Published August 17, 2020
Citation Information: J Clin Invest. 2020;130(9):5011-5026. https://doi.org/10.1172/JCI135536.
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Research Article Nephrology Article has an altmetric score of 63

p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease

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Abstract

Dysregulation of autophagy in diabetic kidney disease (DKD) has been reported, but the underlying mechanism and its pathogenic role remain elusive. We show that autophagy was inhibited in DKD models and in human diabetic kidneys. Ablation of autophagy-related gene 7 (Atg7) from kidney proximal tubules led to autophagy deficiency and worse renal hypertrophy, tubular damage, inflammation, fibrosis, and albuminuria in diabetic mice, indicating a protective role of autophagy in DKD. Autophagy impairment in DKD was associated with the downregulation of unc-51–like autophagy-activating kinase 1 (ULK1), which was mediated by the upregulation of microRNA-214 (miR-214) in diabetic kidney cells and tissues. Ablation of miR-214 from kidney proximal tubules prevented a decrease in ULK1 expression and autophagy impairment in diabetic kidneys, resulting in less renal hypertrophy and albuminuria. Furthermore, blockade of p53 attenuated miR-214 induction in DKD, leading to higher levels of ULK1 and autophagy, accompanied by an amelioration of DKD. Compared with nondiabetic samples, renal biopsies from patients with diabetes showed induction of p53 and miR-214, associated with downregulation of ULK1 and autophagy. We found a positive correlation between p53/miR-214 and renal fibrosis, but a negative correlation between ULK1/LC3 and renal fibrosis in patients with diabetes. Together, these results identify the p53/miR-214/ULK1 axis in autophagy impairment in diabetic kidneys, pinpointing possible therapeutic targets for DKD.

Authors

Zhengwei Ma, Lin Li, Man J. Livingston, Dongshan Zhang, Qingsheng Mi, Ming Zhang, Han-Fei Ding, Yuqing Huo, Changlin Mei, Zheng Dong

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2009 Total
Citations: 11 22 30 22 14 2 1 102
Citation information
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Citations to this article in year 2021 (14)

Title and authors Publication Year
Autophagy in major human diseases
DJ Klionsky, G Petroni, RK Amaravadi, EH Baehrecke, A Ballabio, P Boya, JM Pedro, K Cadwell, F Cecconi, AM Choi, ME Choi, CT Chu, P Codogno, MI Colombo, AM Cuervo, V Deretic, I Dikic, Z Elazar, EL Eskelinen, GM Fimia, DA Gewirtz, DR Green, M Hansen, M Jäättelä, T Johansen, G Juhász, V Karantza, C Kraft, G Kroemer, NT Ktistakis, S Kumar, C LopezOtin, KF Macleod, F Madeo, J Martinez, A Meléndez, N Mizushima, C Münz, JM Penninger, RM Perera, M Piacentini, F Reggiori, DC Rubinsztein, KM Ryan, J Sadoshima, L Santambrogio, L Scorrano, HU Simon, AK Simon, A Simonsen, A Stolz, N Tavernarakis, SA Tooze, T Yoshimori, J Yuan, Z Yue, Q Zhong, L Galluzzi, F Pietrocola
The EMBO Journal 2021
Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions
CD Gonzalez, MP Negueruela, CN Santamarina, R Resnik, MI Vaccaro
Cells 2021
FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys
M Zeng, J Wen, Z Ma, L Xiao, Y Liu, S Kwon, Y Liu, Z Dong
Diabetes 2021
Metformin attenuates renal tubulointerstitial fibrosis via upgrading autophagy in the early stage of diabetic nephropathy
F Wang, H Sun, B Zuo, K Shi, X Zhang, C Zhang, D Sun
Scientific Reports 2021
IFT88 deficiency in proximal tubular cells exaggerates cisplatin-induced injury by suppressing autophagy
S Wang, S Zhuang, Z Dong
American journal of physiology. Renal physiology 2021
Epigenetics and Inflammation in Diabetic Nephropathy
BY Shao, SF Zhang, HD Li, XM Meng, HY Chen
Frontiers in physiology 2021
Glucose Metabolism in Acute Kidney Injury and Kidney Repair
L Wen, Y Li, S Li, X Hu, Q Wei, Z Dong
Frontiers in Medicine 2021
The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin
YY Chen, CH Chen, WC Lin, CW Tung, YC Chen, SH Yang, BM Huang, RJ Chen
Molecules (Basel, Switzerland) 2021
Classical molecule in diabetic kidney hypertrophy is linked to defects in self‐eating through fine‐tuning
Y Takagaki, K Kanasaki
Journal of Diabetes Investigation 2021
Regulation of autophagy by miRNAs in human diseases
SG Roy
The Nucleus 2021
Renal Cellular Autophagy in Obesity: Boon or Bane?
R Ghandriz, LO Lerman
Seminars in Nephrology 2021
miR‑214 ameliorates sepsis‑induced acute kidney injury via PTEN/AKT/mTOR‑regulated autophagy
Z Sang, S Dong, P Zhang, Y Wei
Molecular medicine reports 2021
Proximal Tubule p53 in Cold Storage/Transplantation-Associated Kidney Injury and Renal Graft Dysfunction
X Xiang, J Zhu, G Zhang, Z Ma, MJ Livingston, Z Dong
Frontiers in Medicine 2021
ULK1 Inhibition as a Targeted Therapeutic Strategy for Psoriasis by Regulating Keratinocytes and Their Crosstalk With Neutrophils
X Qiu, L Zheng, X Liu, D Hong, M He, Z Tang, C Tian, G Tan, S Hwang, Z Shi, L Wang
Frontiers in immunology 2021

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