KMUP-1 attenuates high glucose and transforming growth factor-β1-induced pro-fibrotic proteins in mesangial cells

Lin,Sheng‑Hsuan; Chen,Ing‑Jun; Chuang,Chao‑Tang; Ho,Wan‑Ting; Chuang,Lea‑Yea; Guh,Jinn‑Yuh

doi:10.3892/mmr.2017.6486

KMUP-1 attenuates high glucose and transforming growth factor-β1-induced pro-fibrotic proteins in mesangial cells

Authors:
- Sheng‑Hsuan Lin
- Ing‑Jun Chen
- Chao‑Tang Chuang
- Wan‑Ting Ho
- Lea‑Yea Chuang
- Jinn‑Yuh Guh
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Affiliations: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C.
Published online on: April 20, 2017 https://doi.org/10.3892/mmr.2017.6486
Pages: 4199-4206

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Abstract

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.

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