التفاصيل البيبلوغرافية
| العنوان: |
Targeted degradation of LRG1 to attenuate renal fibrosis |
| المؤلفون: |
Linyao Fan, Yingqiu Qi, Xi Yang, Yarui Xu, Yana Zhang, Longdi Wang, Anying Zhu, Lirong Zhang, Jian Song, Shengnan Du, Guangjun Nie, Huan Min |
| المصدر: |
Asian Journal of Pharmaceutical Sciences, Vol 19, Iss 4, Pp 100941- (2024) |
| بيانات النشر: |
Elsevier, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: |
LRG1, Renal fibrosis, Proteolysis targeting chimera, Targeting peptide, Therapeutics. Pharmacology, RM1-950 |
| الوصف: |
Leucine-rich α-2 glycoprotein 1 (LRG1), a secreted glycoprotein, has been identified as significantly upregulated in renal fibrosis, potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways. Herein, utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement, we developed an advanced proteolysis targeting chimera, ETTAC-2, specifically designed for LRG1 degradation. Our cellular degradation assays validated that ETTAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism, achieving half-maximal degradation at a concentration of 8.38 µM. Furthermore, anti-fibrotic experiments conducted both in vitro and in vivo revealed that ETTAC-2 efficiently induced LRG1 degradation in fibrotic kidneys. This action effectively inhibited the TGF-β-Smad3 signaling pathway and diminished the secretion of fibrosis-associated proteins, consequently attenuating the progression of renal fibrosis. Our study highlights the pivotal role of LRG1 in renal fibrosis and positions ETTAC-2 as a promising therapeutic candidate for targeted LRG1 intervention. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1818-0876 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S1818087624000588; https://doaj.org/toc/1818-0876 |
| DOI: |
10.1016/j.ajps.2024.100941 |
| URL الوصول: |
https://doaj.org/article/7c5d685097444fa1801f287319c7903f |
| رقم الانضمام: |
edsdoj.7c5d685097444fa1801f287319c7903f |
| قاعدة البيانات: |
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