title: Leptin promotes endothelial dysfunction in chronic kidney disease through AKT/GSK3β and β-catenin signals.
abstract: Endothelial dysfunction (ED) is a well-recognized instigator of cardiovascular diseases and develops in chronic kidney disease (CKD) with high rate. Recent studies have implicated that leptin is associated with endothelial dysfunction. We investigated the relationship between leptin and markers of ED in CKD patients and how leptin contributed to endothelial damage. 140 CKD patients and 140 healthy subjects were studied. Serum leptin levels were significantly higher in CKD than in controls and displayed significantly positive association with the increase levels of sICAM-1 and sVCAM-1 but negative correlation with flow-mediated dilatation (FMD) reduction in patients. Our in vitro study demonstrated that leptin induced overexpression of ICAM-1 and VCAM-1, led to f-actin reorganization and vinculin assembly, increased endothelial monolayer permeability for FITC-dextran, and accelerated endothelial cell migration; these changes were markedly reversed when the cells were transfected with AKT or β-catenin shRNA vectors. Notably, high leptin resulted in hyper-phosphorylation of AKT and GSK3β, along with nuclear accumulation of β-catenin. In conclusion, serum leptin was elevated in CKD patients and it might contribute to endothelial dysfunction by disarrangement of f-actin cytoskeleton via a mechanism involving the AKT/GSK3β and β-catenin pathway.
authors: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors: Nannan
authors: N
authors: Ding
authors: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors: Bing
authors: B
authors: Liu
authors: Department of Ultrasonography, Shandong Provincial Hospital Affiliated to Shandong University, China.
authors: Jiaguang
authors: J
authors: Song
authors: Department of Ultrasonography, Shandong Medical Imaging Research Institute, Shandong University, China.
authors: Shougang
authors: S
authors: Bao
authors: Department of Pathology, Medical School of Shandong University, Jinan, China.
authors: Junhui
authors: J
authors: Zhen
authors: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: sdlvzhimei@163.com.
authors: Zhimei
authors: Z
authors: Lv
authors: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: Wangrong_sd@126.com.
authors: Rong
authors: R
authors: Wang
mesh_terms: D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D014655:Vascular Resistance; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D020738:Leptin; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT pathway; Chronic kidney disease; Endothelial dysfunction; F-actin remodeling; Leptin