title: miR-24 suppression of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage.
abstract: The regulatory transcriptional factor PATZ1 is abnormally up-regulated in diabetic endothelial cells (ECs) where it acts as an anti-angiogenic factor via modulation of fatty acid-binding protein 4 (FABP4) signaling. The aim of the present work was to elucidate the upstream molecular events regulating PATZ1 expression in diabetic angiogenesis. The bioinformatics search for microRNAs (miRNAs) able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-24 since the multiple targets of miR-24, which have so far been identified in beta cells, cardiomyocytes and macrophages, are all involved in diabetic complications. miR-24 expression was significantly impaired in the ECs isolated from diabetic hearts. Functionally, endothelial migration was profoundly inhibited by miR-24 suppression in Ctrl ECs, whereas miR-24 overexpression by mimics treatment effectively restored the migration rate in diabetic ECs. Mechanistically, miR-24 directly targeted the 3'untranslated region (3'UTR) of PATZ1, and miR-24 accumulation potentiated endothelial migration by reducing the mRNA stability of PATZ1. Together, these results suggest a novel mechanism regulating endothelial PATZ1 expression based on the down-regulation of miR-24 expression caused by hyperglycemia. Interfering with PATZ1 expression via miRNAs or miRNA mimics could potentially represent a new way to target endothelial PATZ1-dependent signaling of vascular dysfunction in diabetes.
authors.affiliation: Department of Clinical Laboratory, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Qingdao 266000, Shandong Province, China.
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Cui
authors.affiliation: Department of Clinical Laboratory, Qingdao Chest Hospital, Qingdao 266000, Shandong Province, China.
authors.forename: Yu-Zhong
authors.initials: YZ
authors.lastname: Hua
authors.affiliation: Department of Clinical Laboratory, Qingdao Jiaozhou District Central Hospital, Qingdao 266000, Shandong Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Qingdao 266000, Shandong Province, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Qingdao 266000, Shandong Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Qingdao 266000, Shandong Province, China.
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Qingdao Huangdao District Hospital of Traditional Chinese Medicine, Qingdao 266000, Shandong Province, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Xi'an Health Management Service Center, Xi'an 710032, Shaanxi Province, China.
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Yan
authors.affiliation: Department of Clinical Laboratory, Heze Hospital of Traditional Chinese Medicine, Heze 274900, Shandong Province, China.
authors.forename: Yang-Guo
authors.initials: YG
authors.lastname: Ma
authors.affiliation: Department of Clinical Laboratory, Juye County People's Hospital, Heze 274900, Shandong Province, China. Electronic address: cyh4800@163.com.
authors.forename: Yun-He
authors.initials: YH
authors.lastname: Cao
authors.affiliation: Department of Clinical Laboratory, Heze Municipal Hospital, Heze 274031, Shandong Province, China. Electronic address: zxhhzslyy@163.com.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000071757:BTB-POZ Domain; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C485875:Zfp278 protein, mouse
keywords: Angiogenesis; Diabetes; Endothelial cells; PATZ1; miR-24