Upregulated DJ-1 Promotes Renal Tubular EMT by Suppressing Cytoplasmic PTEN Expression and Akt Activation

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 31; no. 4; pp. 469 - 475
• Main Author: 姚颖 位红兰 刘丽丽 刘琳 白寿军 李彩霞 罗云 曾锐 韩敏 葛树旺 徐钢
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.08.2011
• Subjects: Akt; Animals; Cell Line; Cytoplasm - genetics; EMT; Humans; Intracellular Signaling Peptides and Proteins - genetics; Kidney Tubules, Proximal - metabolism; Male; Medicine; Medicine & Public Health; Oncogene Proteins - genetics; Organic Cation Transport Proteins - genetics; Protein Deglycase DJ-1; Proto-Oncogene Proteins c-akt - genetics; PTEN Phosphohydrolase - genetics; PTEN基因; Rats; Rats, Sprague-Dawley; Up-Regulation - genetics; 基因表达; 激活; 细胞质; 肾小管上皮细胞; 转化生长因子-β1; DJ-1; epithelial-mesenchymal transition; Akt; transforming growth factor-beta 1; phosphatase and tensin homolog deleted on chromosome 10
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-011-0475-3

Recently,phosphatase and tensin homolog deleted on chromosome 10（PTEN） is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells（HKC） were treated with transforming growth factor-beta 1（TGF-β1）,or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase（PI3K） inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition（EMT） and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.