Abstract: SA-PO853
Newly Designed Recombinant Bone Morphogenetic Protein 7 Is a Potential Therapeutic in Renal Tubulointerstitial Fibrosis
Session Information
- Molecular Mechanisms of CKD - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Park, Jimin, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Kang, Sukyung, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Nam, Boyoung, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Choi, Arum, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
Background
Renal tubulointerstitial fibrosis, final common mechanism for all kidney diseases, is characterized by extracellular matrix (ECM) accumulation. In addition, transforming growth factor-β1 (TGF-β1) is known to plays a principal mediator in the accumulation of ECM. Bone morphogenetic protein-7 (BMP-7) is counteract of the profibrogenic role of TGF-β1. Recently, our group designed recombinant BMP-7 linked by protein transduction domain (PTD), which has capability to effectively deliver a large molecule protein in eukaryotic cells. In this study, we investigated the effect of PTD-mediated BMP-7 (tissue-regeneration polypeptide 2, TRP2) on renal tubulointerstitial fibrosis.
Methods
In vitro, inner medullary collecting duct cells (IMCDs) were cultured in DMEM/F12 media (Control) or TGF-β1 (5 ng/ml) with or without TRP2 (10 ng/ml) for 48 hours. In vivo, tubule-interstitial fibrosis were established by unilateral ureteral obstruction (UUO) in C57BL/6 mice, and TRP2 (1 µg) were directly injected intraureterally after UUO operation, and were sacrificed after 7 days. The protein expression of fibronectin, type I collagen (ColI), and α-smooth muscle actin (αSMA) were determined in cultured IMCDs and the kidneys by western blot analysis. Masson’s trichrome staining and immunohistochemistry were also evaluated in the mouse kidneys.
Results
Xpress, reporter protein of TRP2, was expressed in TRP2-treated IMCDs after 2 hours in dose-dependent manner. Compared to control, the expression of fibronectin, ColI, and αSMA were significantly increased in TGF-β1-stimulated IMCDs. These changes in cultured IMCDs exposed to TGF-β1 were significantly abrogated by TRP2 treatment. A significant increase in ECM proteins expression was also observed in the kidney of UUO mice compared to the control group kidney. These changes were significantly ameliorated in TRP2-treated group.
Conclusion
These results suggest that TRP2 is directly suppressing the process of TGF-β1-induced ECM accumulation in vitro and in vivo. The effect of TRP2 can be promising potential therapeutic for prevention of renal tubulointerstitial fibrosis in various kidney diseases.