International Journal Of Bilogical Sciences
.: Home > International Journal Of Bilogical Sciences > 2016 > Volume 12 Number 5 > Yang Zhang1, Kun Ling Ma1 Corresponding address, Xiong Zhong Ruan2, Bi Cheng Liu1
Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury
Yang Zhang1, Kun Ling Ma1 Corresponding address, Xiong Zhong Ruan2, Bi Cheng Liu1
1. Institute of Nephrology, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing City, Jiangsu Province, China. 2. Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, UK. Corresponding author: Kun Ling Ma. Institute of Nephrology, Zhong Da Hospital, School of Medicine, Southeast University, NO. 87, Ding Jia Qiao Road, Nan Jing City, Jiangsu Province, China, 210009. Tel: 0086 25 83262442 Fax: 0086 25 83262442 E-mail: Kun Ling Ma: firstname.lastname@example.org
The low-density lipoprotein receptor (LDLR) pathway is a negative feedback system that plays important roles in the regulation of plasma and intracellular cholesterol homeostasis. To maintain a cholesterol homeostasis, LDLR expression is tightly regulated by sterol regulatory element-binding protein-2 (SREBP-2) and SREBP cleavage-activating protein (SCAP) in transcriptional level and by proprotein convertase subtilisin/kexin type 9 (PCSK9) in posttranscriptional level. The dysregulation of LDLR expression results in abnormal lipid accumulation in cells and tissues, such as vascular smooth muscle cells, hepatic cells, renal mesangial cells, renal tubular cells and podocytes. It has been demonstrated that inflammation, renin-angiotensin system (RAS) activation, and hyperglycemia induce the disruption of LDLR pathway, which might contribute to lipid disorder-mediated organ injury (atherosclerosis, non-alcoholic fatty liver disease, kidney fibrosis, etc). The mammalian target of rapamycin (mTOR) pathway is a critical mediator in the disruption of LDLR pathway caused by pathogenic factors. The mTOR complex1 activation upregulates LDLR expression at the transcriptional and posttranscriptional levels, consequently resulting in lipid deposition. This paper mainly reviews the mechanisms for the dysregulation of LDLR pathway and its roles in lipid disorder-mediated organ injury under various pathogenic conditions. Understanding these mechanisms leading to the abnormality of LDLR expression contributes to find potential new drug targets in lipid disorder-mediated diseases.
dysregulation, low-density lipoprotein receptor, cholesterol homeostasis, lipid disorder, organ injury.
Date Deposited : 04 Nov 2016 21:40
Official URL: http://www.ijbs.com/v12i5
Last Modified : 04 Nov 2016 21:40
Volume 12, Number 5, March 2016
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