Angiotensin II induces cholesterol accumulation and injury in podocytes.
作者： Yingjie Yang , Qian Yang , Jian Yang , Yiqiong Ma , Guohua Ding
DOI: 10.1038/S41598-017-09733-W
关键词: Cholesterol 、 ABCA1 、 Podocyte 、 Angiotensin II 、 Endocrinology 、 Lipid droplet 、 Losartan 、 Internal medicine 、 Lipid metabolism 、 LDL receptor 、 Chemistry
摘要: Angiotensin II (Ang II) is a risk factor for the initiation and progression of chronic kidney disease (CKD), as elevated Ang levels can lead to podocyte injury. However, there have been no studies on role in lipid metabolism or injury caused by dysfunction. Our study showed that induced droplet (LD) accumulation expression LD marker adipose differentiation-related protein (ADRP) podocytes, extent deposition could be alleviated losartan. also demonstrated increased content cholesterol which an component, this change was accompanied decreased efflux-related molecule ATP-binding cassette transporter-1 (ABCA1) uptake-related LDL receptor (LDLR) synthesis-related molecules sterol regulatory element-binding (SREBP1 SREBP2) 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). Pretreating podocytes with methyl-β-cyclodextrin (CD), induces efflux, II-mediated II-induced apoptosis maintained cytoskeleton spreading. These results suggested regulating metabolism-related subsequent dysfunction resulted
nature.com
harvard.edu
pubmed.cn参考文章(30)
Sandra Merscher, Christopher E. Pedigo, Armando J. Mendez, Metabolism, energetics, and lipid biology in the podocyte - cellular cholesterol-mediated glomerular injury Frontiers in Endocrinology. ,vol. 5, pp. 169- 169 ,(2014) , 10.3389/FENDO.2014.00169
Bernhard Schermer, Thomas Benzing, Lipid–Protein Interactions along the Slit Diaphragm of Podocytes Journal of The American Society of Nephrology. ,vol. 20, pp. 473- 478 ,(2009) , 10.1681/ASN.2008070694
Hae-Young Lee, Ichiro Sakuma, Sang-Hyun Ihm, Choong-Won Goh, Kwang Kon Koh, Statins and renin-angiotensin system inhibitor combination treatment to prevent cardiovascular disease Circulation. ,vol. 78, pp. 281- 287 ,(2014) , 10.1253/CIRCJ.CJ-13-1494
Nathan E. Wolins, Benjamin K. Quaynor, James R. Skinner, Marissa J. Schoenfish, Anatoly Tzekov, Perry E. Bickel, S3-12, Adipophilin, and TIP47 Package Lipid in Adipocytes Journal of Biological Chemistry. ,vol. 280, pp. 19146- 19155 ,(2005) , 10.1074/JBC.M500978200
Kun-Ling Ma, Jie Ni, Chang-Xian Wang, Jing Liu, Yang Zhang, Yu Wu, Lin-Li Lv, Xiong-Zhong Ruan, Bi-Cheng Liu, Interaction of RAS activation and lipid disorders accelerates the progression of glomerulosclerosis. International Journal of Medical Sciences. ,vol. 10, pp. 1615- 1624 ,(2013) , 10.7150/IJMS.6635
Tobias B Huber, Bernhard Schermer, Roman Ulrich Müller, Martin Höhne, Malte Bartram, Andrea Calixto, Henning Hagmann, Christian Reinhardt, Fabienne Koos, Karl Kunzelmann, Elena Shirokova, Dietmar Krautwurst, Christian Harteneck, Matias Simons, Hermann Pavenstädt, Dontscho Kerjaschki, Christoph Thiele, Gerd Walz, Martin Chalfie, Thomas Benzing, Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 103, pp. 17079- 17086 ,(2006) , 10.1073/PNAS.0607465103
Chongren Tang, Jenny E. Kanter, Karin E. Bornfeldt, Renee C. Leboeuf, John F. Oram, Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneys. Journal of Lipid Research. ,vol. 51, pp. 1719- 1728 ,(2010) , 10.1194/JLR.M003525
Cesar A. López, Alex H. de Vries, Siewert J. Marrink, Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction PLoS Computational Biology. ,vol. 7, pp. e1002020- ,(2011) , 10.1371/JOURNAL.PCBI.1002020
Alessia Fornoni, Sandra Merscher, Jeffrey B. Kopp, Lipid biology of the podocyte—new perspectives offer new opportunities Nature Reviews Nephrology. ,vol. 10, pp. 379- 388 ,(2014) , 10.1038/NRNEPH.2014.87
Raghu V. Durvasula, Stuart J. Shankland, The renin-angiotensin system in glomerular podocytes: mediator of glomerulosclerosis and link to hypertensive nephropathy. Current Hypertension Reports. ,vol. 8, pp. 132- 138 ,(2006) , 10.1007/S11906-006-0009-8