title: Wnt/β-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy.
abstract: Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR. Kidney biopsies of DN patients and health individuals were stained by immunofluorescence (IF) method. The morphological and functional changes of podocytes were tested by F-actin staining and cell migration assay. Results demonstrated that HG induced upregulation of UCH-L1 and activation of the Wnt/β-catenin signaling pathway in podocytes. However, blocking of the Wnt pathway by dickkopf related protein 1 (DKK1) eliminated the above changes. Furthermore, IF staining confirmed that, compared with healthy individuals, the expression of UCH-L1 and β-catenin were obviously increased in kidney biopsy of DN patients. Overexpression of UCH-L1 remodeled its actin cytoskeleton, increased its cell migration and impacted its important proteins. All the findings manifested that Wnt/β-catenin/UCH-L1 may be a new potential therapy method in the treatment of DN in future.
authors: Department of Clinic Pathology, Weifang Medical University, Weifang 261053, China. zhanghx@wfmc.edu.cn.
authors: Hongxia
authors: H
authors: Zhang
authors: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. luoweililuoweili@163.com.
authors: Weili
authors: W
authors: Luo
authors: Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang 261031, China. sunyonghong88@163.com.
authors: Yonghong
authors: Y
authors: Sun
authors: Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang 261031, China. yan7902@163.com.
authors: Yanchun
authors: Y
authors: Qiao
authors: Department of Clinic Pathology, Weifang Medical University, Weifang 261053, China. liying7h@163.com.
authors: Liying
authors: L
authors: Zhang
authors: Department of Pathology, Maternal and Child Care Service Centre of Changyi, Changyi 261300, China. 15963622065@163.com.
authors: Zhilian
authors: Z
authors: Zhao
authors: Department of Clinic Pathology, Weifang Medical University, Weifang 261053, China. sjlu@wfmc.edu.cn.
authors: Shijun
authors: S
authors: Lv
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000199:Actins; D043222:Ubiquitin Thiolesterase; D005947:Glucose
keywords: DN; UCH-L1; Wnt/β-catenin; podocytes