Academic Journal
Benzbromarone Induces Targeted Degradation of HSP47 Protein and Improves Hypertrophic Scar Formation
| العنوان: | Benzbromarone Induces Targeted Degradation of HSP47 Protein and Improves Hypertrophic Scar Formation |
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| المؤلفون: | Park, Jung Gyu, Lim, Dong Chul, Park, Jeong Hwan, Park, Seoah, Mok, Jongsoo, Kang, Keon Wook, Park, Joonghoon |
| المساهمون: | Kang, Keon Wook, Park, Joonghoon |
| بيانات النشر: | Elsevier Inc. |
| سنة النشر: | 2024 |
| المجموعة: | Seoul National University: S-Space |
| مصطلحات موضوعية: | A-COUPLED LIPOSOMES, CHAPERONE HSP47, ENDOPLASMIC-RETICULUM, MOLECULAR CHAPERONE, COLLAGEN, FIBROSIS, MECHANISMS, SIRNA, PROCOLLAGEN, RESOLUTION, Benzbromarone, HSP47, Hypertrophic scar, Targeted protein degrader |
| الوصف: | Fibrotic diseases are characterized by the abnormal accumulation of collagen in the extracellular matrix, leading to the functional impairment of various organs. In the skin, excessive collagen deposition manifests as hypertrophic scars and keloids, placing a substantial burden on patients and the healthcare system worldwide. HSP47 is essential for proper collagen assembly and contributes to fibrosis. However, identifying clinically applicable HSP47 inhibitors has been a major pharmaceutical challenge. In this study, we identified benzbromarone (BBR) as an HSP47 inhibitor for hypertrophic scarring treatment. BBR inhibited collagen production and secretion in fibroblasts from patients with keloid by binding to HSP47 and inhibiting the interaction between HSP47 and collagen. Interestingly, BBR not only inhibits HSP47 but also acts as a molecular glue degrader that promotes its proteasome-dependent degradation. Through these molecular mechanisms, BBR effectively reduced hypertrophic scarring in mini pigs and rats with burns and/or excisional skin damage. Thus, these findings suggest that BBR can be used to clinically treat hypertrophic scars and, more generally, fibrotic diseases. ; Y ; 1 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0022-202X |
| Relation: | Journal of Investigative Dermatology, Vol.144 No.3, pp.633-644; https://hdl.handle.net/10371/205105; 001203099100001; 2-s2.0-85177206173; 205759 |
| DOI: | 10.1016/j.jid.2023.09.279 |
| الاتاحة: | https://hdl.handle.net/10371/205105 https://doi.org/10.1016/j.jid.2023.09.279 |
| رقم الانضمام: | edsbas.896B94D1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 0022202X |
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| DOI: | 10.1016/j.jid.2023.09.279 |