대한신장학회

논문분류	춘계학술대회 초록집
제목	Newly Designed Recombinant Bone Morphogenetic Protein 7 is a Potential Therapeutic in Renal Tubulointerstitial Fibrosis
저자	Seonghun Kim1, Bo Young Nam1, Jimin Park1, Meiyan Wu1, Sukyung Kang1, Arum Choi1, Jung Tak Park2, Seung Hyeok Han2, Shin-Wook Kang2, Tae-Hyun Yoo2
출판정보	2018; 2018(1):
키워드	Protein transduction domain \| Bone morphogenetic protein 7 \| Renal tubulointerstitial fibros \| Extracellular matrix
초록	Objectives: 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. Conclusions: 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.
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