KMUP-1 attenuates high glucose and transforming growth factor-β1-induced pro-fibrotic proteins in mesangial cells
Autor: | Chao‑Tang Chuang, Lea-Yea Chuang, Sheng-Hsuan Lin, Jinn Yuh Guh, Wan‑Ting Ho, Ing‑Jun Chen |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Collagen Type IV Cancer Research medicine.medical_specialty Cell Smad2 Protein Biochemistry Streptozocin Nitric oxide Cell Line Diabetes Mellitus Experimental Histones Transforming Growth Factor beta1 03 medical and health sciences chemistry.chemical_compound Mice Piperidines Internal medicine Genetics medicine Animals Diabetic Nephropathies Smad3 Protein Molecular Biology Oncogene biology Methyltransferases Cell cycle Streptozotocin Molecular biology Fibrosis Fibronectins Fibronectin 030104 developmental biology medicine.anatomical_structure Endocrinology Glucose Oncology chemistry Apoptosis Xanthines Mesangial Cells biology.protein Molecular Medicine Transforming growth factor medicine.drug Signal Transduction |
Zdroj: | Molecular medicine reports. 15(6) |
ISSN: | 1791-3004 |
Popis: | We have previously demonstrated that KMUP-1, a xanthine-based nitric oxide enhancer, attenuates diabetic glomerulosclerosis, while increasing renal endothelial nitric oxide synthase expression in rats. However, the anti‑fibrotic mechanisms of KMUP‑1 treatment in diabetic nephropathy in terms of cell biology and transforming growth factor-β1 (TGF‑β1) remain unclear. Therefore, the present study involved investigating the effects of KMUP‑1 on high glucose (HG) or TGF‑β1‑induced pro‑fibrotic proteins in mouse mesangial (MES13) cells, and the effects of KMUP‑1 on streptozotocin (STZ)‑induced diabetic rats. It was identified that KMUP‑1 (10 µM) attenuated HG (30 mM)‑induced cell hypertrophy while attenuating TGF‑β1 gene transcription and bioactivity in MES13 cells. In addition, KMUP‑1 attenuated TGF‑β1 (5 ng/ml)‑induced Smad2/3 phosphorylation while attenuating HG or TGF‑β1‑induced collagen IV and fibronectin protein expression. Furthermore, KMUP‑1 attenuated HG‑decreased Suv39h1 and H3K9me3 levels. Finally, KMUP‑1 attenuated diabetes-induced collagen IV and fibronectin protein expression in STZ‑diabetic rats at 8 weeks. In conclusion, KMUP‑1 attenuates HG and TGF‑β1‑induced pro‑fibrotic proteins in mesangial cells and attenuation of TGF‑β1‑induced signaling and attenuation of HG‑decreased Suv39h1 expression may be two of the anti-fibrotic mechanisms of KMUP‑1. |
Databáze: | OpenAIRE |
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