Yu Sun1, Sijia Cui1, Yunfeng Hou2, Fan Yi1. 1. The Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China. 2. Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated with Shandong First Medical University, Jinan, China.
Abstract
BACKGROUND: Podocytes, functionally specialized and terminally differentiated glomerular visceral epithelial cells, are critical for maintaining the structure and function of the glomerular filtration barrier. Podocyte injury is considered as the most important early event contributing to proteinuric kidney diseases such as obesity-related renal disease, diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease. Although considerable advances have been made in the understanding of mechanisms that trigger podocyte injury, cell-specific and effective treatments are not clinically available. SUMMARY: Emerging evidence has indicated that the disorder of podocyte lipid metabolism is closely associated with various proteinuric kidney diseases. Excessive lipid accumulation in podocytes leads to cellular dysfunction which is defined as lipotoxicity, a phenomenon characterized by mitochondrial oxidative stress, actin cytoskeleton remodeling, insulin resistance, and inflammatory response that can eventually result in podocyte hypertrophy, detachment, and death. In this review, we summarize recent advances in the understanding of lipids in podocyte biological function and the regulatory mechanisms leading to podocyte lipid accumulation in proteinuric kidney disease. KEY MESSAGES: Targeting podocyte lipid metabolism may represent a novel therapeutic strategy for patients with proteinuric kidney disease.
BACKGROUND: Podocytes, functionally specialized and terminally differentiated glomerular visceral epithelial cells, are critical for maintaining the structure and function of the glomerular filtration barrier. Podocyte injury is considered as the most important early event contributing to proteinuric kidney diseases such as obesity-related renal disease, diabetic kidney disease, focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease. Although considerable advances have been made in the understanding of mechanisms that trigger podocyte injury, cell-specific and effective treatments are not clinically available. SUMMARY: Emerging evidence has indicated that the disorder of podocyte lipid metabolism is closely associated with various proteinuric kidney diseases. Excessive lipid accumulation in podocytes leads to cellular dysfunction which is defined as lipotoxicity, a phenomenon characterized by mitochondrial oxidative stress, actin cytoskeleton remodeling, insulin resistance, and inflammatory response that can eventually result in podocyte hypertrophy, detachment, and death. In this review, we summarize recent advances in the understanding of lipids in podocyte biological function and the regulatory mechanisms leading to podocyte lipid accumulation in proteinuric kidney disease. KEY MESSAGES: Targeting podocyte lipid metabolism may represent a novel therapeutic strategy for patients with proteinuric kidney disease.
Authors: Xiaoxin X Wang; Jonathan Levi; Yuhuan Luo; Komuraiah Myakala; Michal Herman-Edelstein; Liru Qiu; Dong Wang; Yingqiong Peng; Almut Grenz; Scott Lucia; Evgenia Dobrinskikh; Vivette D D'Agati; Hermann Koepsell; Jeffrey B Kopp; Avi Z Rosenberg; Moshe Levi Journal: J Biol Chem Date: 2017-02-14 Impact factor: 5.157
Authors: Carolina E Hagberg; Annika Mehlem; Annelie Falkevall; Lars Muhl; Barbara C Fam; Henrik Ortsäter; Pierre Scotney; Daniel Nyqvist; Erik Samén; Li Lu; Sharon Stone-Elander; Joseph Proietto; Sofianos Andrikopoulos; Ake Sjöholm; Andrew Nash; Ulf Eriksson Journal: Nature Date: 2012-09-26 Impact factor: 49.962
Authors: Yu B Y Sun; Xinli Qu; Victor Howard; Lie Dai; Xiaoyun Jiang; Yi Ren; Ping Fu; Victor G Puelles; David J Nikolic-Paterson; Georgina Caruana; John F Bertram; Mark W Sleeman; Jinhua Li Journal: Kidney Int Date: 2015-05-06 Impact factor: 10.612
Authors: Tae-Hyun Yoo; Christopher E Pedigo; Johanna Guzman; Mayrin Correa-Medina; Changli Wei; Rodrigo Villarreal; Alla Mitrofanova; Farah Leclercq; Christian Faul; Jing Li; Matthias Kretzler; Robert G Nelson; Markku Lehto; Carol Forsblom; Per-Henrik Groop; Jochen Reiser; George William Burke; Alessia Fornoni; Sandra Merscher Journal: J Am Soc Nephrol Date: 2014-06-12 Impact factor: 10.121