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Int J Biol Sci 2016; 12(5):569-579. doi:10.7150/ijbs.14027 This issue Cite

Research Paper

Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury

Yang Zhang1, Kun Ling Ma1✉, 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: More

Citation:
Zhang Y, Ma KL, Ruan XZ, Liu BC. Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury. Int J Biol Sci 2016; 12(5):569-579. doi:10.7150/ijbs.14027. https://www.ijbs.com/v12p0569.htm
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Abstract

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.

Keywords: dysregulation, low-density lipoprotein receptor, cholesterol homeostasis, lipid disorder, organ injury.

Citation styles

APA
Zhang, Y., Ma, K.L., Ruan, X.Z., Liu, B.C. (2016). Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury. International Journal of Biological Sciences, 12(5), 569-579. https://doi.org/10.7150/ijbs.14027.

ACS
Zhang, Y.; Ma, K.L.; Ruan, X.Z.; Liu, B.C. Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury. Int. J. Biol. Sci. 2016, 12 (5), 569-579. DOI: 10.7150/ijbs.14027.

NLM
Zhang Y, Ma KL, Ruan XZ, Liu BC. Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury. Int J Biol Sci 2016; 12(5):569-579. doi:10.7150/ijbs.14027. https://www.ijbs.com/v12p0569.htm

CSE
Zhang Y, Ma KL, Ruan XZ, Liu BC. 2016. Dysregulation of the Low-Density Lipoprotein Receptor Pathway Is Involved in Lipid Disorder-Mediated Organ Injury. Int J Biol Sci. 12(5):569-579.

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