PMID- 32632610 OWN - NLM STAT- MEDLINE DCOM- 20210428 LR - 20231213 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 473 IP - 1-2 DP - 2020 Oct TI - Leptin promotes endothelial dysfunction in chronic kidney disease by modulating the MTA1-mediated WNT/beta-catenin pathway. PG - 155-166 LID - 10.1007/s11010-020-03816-5 [doi] AB - Endothelial dysfunction (ED) has a high incidence in chronic kidney disease (CKD) and is identified as a precursor to cardiovascular events. Recent studies suggest that leptin may be the missing link between ED and CKD. The objective of this study was to investigate the mechanism by which leptin causes ED and the connection with leptin and indicators of ED in CKD patients. Analysis of leptin-treated human umbilical vein endothelial cells (HUVECs) showed increased expression of interleukin 6 (IL-6), endothelin 1 (ET-1) and human monocyte chemoattractant protein 1 (MCP-1), resulting in F-actin recombination and vinculin aggregation as well as endothelial cell migration. In vitro studies have shown that leptin leads to increased WNT1 expression and the accumulation of beta-catenin. Metastasis-associated protein 1 (MTA1), a critical upstream modifier of WNT1 signaling, increased the expression level in leptin-mediated regulation. In contrast, opposite results were observed when cells are transfected with MTA1 or WNT1 shRNA lentivirus vectors. Among 160 patients with CKD and 160 healthy subjects, patients with CKD had significantly higher serum leptin levels than those of the control group, which were positively correlated with increased levels of IL-6, ET-1 and MCP-1. However, these levels were negatively correlated with flow-mediated dilatation (FMD). Hence, these investigations provided novel information on the increased serum leptin levels in CKD patients leading to ED via the MTA1-WNT/beta-catenin pathway. FAU - Liu, Bing AU - Liu B AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Qiao, Jiao AU - Qiao J AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Hu, Jinxiu AU - Hu J AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Fan, Minghua AU - Fan M AD - Department of Obstetrics and Gynecology, The Second Hospital of Shandong University, Jinan, 250021, Shandong, China. FAU - Zhao, Yanfang AU - Zhao Y AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Su, Hong AU - Su H AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Wang, Ziyang AU - Wang Z AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Yu, Qun AU - Yu Q AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Ma, Qiqi AU - Ma Q AD - Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. FAU - Li, Yanmei AU - Li Y AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. FAU - Lv, Zhimei AU - Lv Z AUID- ORCID: 0000-0003-1634-883X AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. sdlvzhimei@163.com. AD - Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. sdlvzhimei@163.com. FAU - Wang, Rong AU - Wang R AD - Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China. Wangrong_sd@126.com. AD - Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. Wangrong_sd@126.com. LA - eng GR - 81770723/National Natural Science Foundation of China/ GR - 81370834/National Natural Science Foundation of China/ GR - 81873615/National Natural Science Foundation of China/ GR - 81400732/National Natural Science Foundation of China/ GR - 201805001/The Science and Technology Innovation Program of Clinical Medicine from the Jinan Science and Technology Bureau/ GR - 201805054/The Science and Technology Innovation Program of Clinical Medicine from the Jinan Science and Technology Bureau/ GR - ts201712090/Taishan Scholars Program of Shandong Province/ GR - tsqn201812138/Taishan Scholars Program of Shandong Province/ PT - Clinical Trial PT - Journal Article DEP - 20200706 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (CTNNB1 protein, human) RN - 0 (LEP protein, human) RN - 0 (Leptin) RN - 0 (MTA1 protein, human) RN - 0 (Repressor Proteins) RN - 0 (Trans-Activators) RN - 0 (beta Catenin) SB - IM MH - Adult MH - Endothelium, Vascular/*metabolism/pathology MH - Female MH - Human Umbilical Vein Endothelial Cells/*metabolism/pathology MH - Humans MH - Leptin/*metabolism MH - Male MH - Middle Aged MH - Renal Insufficiency, Chronic/*metabolism/pathology MH - Repressor Proteins/*metabolism MH - Trans-Activators/*metabolism MH - *Wnt Signaling Pathway MH - beta Catenin/metabolism OTO - NOTNLM OT - Chronic kidney disease OT - Endothelial dysfunction OT - Leptin OT - Metastasis-associated protein 1 OT - Wnt/beta-catenin pathway EDAT- 2020/07/08 06:00 MHDA- 2021/04/29 06:00 CRDT- 2020/07/08 06:00 PHST- 2020/01/22 00:00 [received] PHST- 2020/06/25 00:00 [accepted] PHST- 2020/07/08 06:00 [pubmed] PHST- 2021/04/29 06:00 [medline] PHST- 2020/07/08 06:00 [entrez] AID - 10.1007/s11010-020-03816-5 [pii] AID - 10.1007/s11010-020-03816-5 [doi] PST - ppublish SO - Mol Cell Biochem. 2020 Oct;473(1-2):155-166. doi: 10.1007/s11010-020-03816-5. Epub 2020 Jul 6.