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Engineering of a Long-Acting Bone Morphogenetic Protein-7 by Fusion with Albumin for the Treatment of Renal Injury.
Takano, Mei; Toda, Shota; Watanabe, Hiroshi; Fujimura, Rui; Nishida, Kento; Bi, Jing; Minayoshi, Yuki; Miyahisa, Masako; Maeda, Hitoshi; Maruyama, Toru.
Afiliación
  • Takano M; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Toda S; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Watanabe H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Fujimura R; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Nishida K; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Bi J; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Minayoshi Y; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Miyahisa M; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Maeda H; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
  • Maruyama T; Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Pharmaceutics ; 14(7)2022 Jun 24.
Article en En | MEDLINE | ID: mdl-35890230
The bone morphogenetic protein-7 (BMP7) is capable of inhibiting TGF-ß/Smad3 signaling, which subsequently results in protecting the kidney from renal fibrosis, but its lower blood retention and osteogenic activity are bottlenecks for its clinical application. We report herein on the fusion of carbohydrate-deficient human BMP7 and human serum albumin (HSA-BMP7) using albumin fusion technology and site-directed mutagenesis. When using mouse myoblast cells, no osteogenesis was observed in the glycosylated BMP7 derived from Chinese hamster ovary cells in the case of unglycosylated BMP7 derived from Escherichia coli and HSA-BMP7. On the contrary, the specific activity for the Smad1/5/8 phosphorylation of HSA-BMP7 was about 25~50-times lower than that for the glycosylated BMP7, but the phosphorylation activity of the HSA-BMP7 was retained. A pharmacokinetic profile showed that the plasma half-life of HSA-BMP7 was similar to that for HSA and was nearly 10 times longer than that of BMP7. In unilateral ureteral obstruction mice, weekly dosing of HSA-BMP7 significantly attenuated renal fibrosis, but the individual components, i.e., HSA or BMP7, did not. HSA-BMP7 also attenuated a cisplatin-induced acute kidney dysfunction model. The findings reported herein indicate that HSA-BMP7 has the potential for use in clinical applications for the treatment of renal injuries.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Pharmaceutics Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Pharmaceutics Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza