title: PTEN ameliorates high glucose-induced lipid deposits through regulating SREBP-1/FASN/ACC pathway in renal proximal tubular cells.
abstract: Phosphatase and tensin homology deleted on chromosome ten (PTEN) is a negative regulator of PI3K/Akt pathway, and here we investigated the effect of PTEN on lipogenesis in diabetic rats and high glucose-stimulated human renal proximal tubular cell line (HKC). Decreased PTEN and increased phospho-Akt were found in kidney of diabetic rats, and in vitro research revealed that high glucose attenuated PTEN expression in a time-dependent manner, concomitant with activation of Akt. Again, expression of PTEN significantly inhibited high glucose-caused increased phospho-Akt and lipogenic genes including SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Furthermore, we confirmed inhibition of TGF-β1 pathway with SB431542 blocked the effect of high glucose on PTEN down-regulation, an increase in phospho-Akt and lipogenesis. These above data suggest that decreased PTEN mediates high glucose-induced lipogenesis in renal proximal tubular cells and TGF-β1 might be involved in PTEN down-regulation.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D050155:Lipogenesis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D013549:Sweetening Agents; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005947:Glucose