title: Phospho-GSK-3β is involved in the high-glucose-mediated lipid deposition in renal tubular cells in diabetes.
abstract: The phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway mediates the high-glucose-induced lipid accumulation in the renal tubular cells in diabetes. Studies have revealed that the downstream target genes of phospho-Akt, BCL2-associated death promoter (Bad) and glycogen synthase kinase-3β (GSK-3β) are associated with lipid accumulation in hepatic cells and preadipocytes. In the present study, it was revealed that the phospho-Akt, phospho-Bad, phosphor-GSK-3β contents and lipogenesis were increased in the renal tubular cells of diabetic rats. However, in high-glucose-treated human renal tubular cells, only the phospho-GSK-3β content increased without an alteration in the phospho-Bad content, which could be reversed by treatment with a short hairpin RNA vector aimed at Akt. Inhibiting GSK-3β activity using TWS119 increased the sterol regulatory element binding protein-1 (SREBP-1) content and lipogenesis in renal tubular cells. Furthermore, the exogenous expression of wild-type GSK-3β enhanced the level of phospho-GSK-3β in high-glucose-stimulated renal tubular cells, followed by increased SREBP-1 expression and lipogenesis. Moreover, exogenous expression of mutant GSK-3β (via vector S9A) prevented the increase in SREBP-1 expression and cellular lipogenesis by decreasing the phospho-GSK-3β content and increasing the GSK-3β activity in high-glucose-treated cells. These data suggested that phospho-GSK-3β is involved in the high-glucose-mediated increase of SREBP-1 expression and triglyceride content in renal tubular cells in diabetes.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism
chemical_list: C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Bad; GSK-3β; Lipid metabolism; PI3K/Akt pathway; SREBP-1