Arginine-Rich Peptides Regulate the Pathogenic Galectin-10 Crystallization and Mitigate Crystallopathy-Associated Inflammation

被引：0

作者：

Zhang, Wenbo ^{[1
]}

Li, Shuyuan ^{[1
]}

Wang, Yang ^{[1
,2
]}

Liu, Shuli ^{[3
]}

Liu, Lei ^{[4
,5
]}

Deng, Zhun ^{[1
]}

Mo, Shanshan ^{[1
]}

Chen, Mingrui ^{[1
]}

Li, Zhenyan ^{[1
]}

Wang, Ruonan ^{[1
]}

Zhou, Xin ^{[1
]}

Xu, Longxin ^{[1
]}

Yu, Lanlan ^{[1
]}

Liu, Zhenlin ^{[6
]}

Li, Hongwei ^{[7
]}

Liang, Junbo ^{[8
]}

Wang, Chenxuan ^{[1
]}

机构：

[1] Chinese Acad Med Sci, Dept Biophys & Struct Biol, State Key Lab Common Mech Res Major Dis, Haihe Lab Cell Ecosyst,Inst Basic Med Sci,Sch Basi, Beijing 100005, Peoples R China

[2] Peking Univ Hlth Sci Ctr, Inst Cardiovasc Sci, Sch Basic Med Sci, State Key Lab Vasc Homeostasis & Remodeling, Beijing 100191, Peoples R China

[3] Peking Univ Civil Aviat, Dept Clin Lab, Sch Clin Med, Beijing 100123, Peoples R China

[4] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[5] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[6] Peking Univ Third Hosp, Dept Med Engn, Beijing 100191, Peoples R China

[7] Peking Univ, Beijing Nucl Magnet Resonance Ctr, Beijing 100871, Peoples R China

[8] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Ctr Bioinformat,Dept Biochem & Mol Biol,Sch Basic, Beijing 100005, Peoples R China

来源：

ACS APPLIED MATERIALS & INTERFACES | 2025年 / 17卷 / 06期

基金：

国家重点研发计划; 北京市自然科学基金; 中国国家自然科学基金;

关键词：

protein assembly; protein aggregation; peptide; intermolecularinteractions; interface; CRYSTALS ACTIVATE; NASAL POLYP; PROTEIN; BINDING; INSTILLATION; MECHANISMS; MODEL;

D O I：

10.1021/acsami.4c18411

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Protein self-assembly into a crystal in vivo triggers acute or chronic organ injury that can lead to intractable diseases lacking specific treatment options. In this study, we report the discovery of ionic arginine-rich peptides to disrupt the pathogenic galectin-10 (gal-10) crystallization, where the aberrant deposition of gal-10 crystals in airways causes the activation of IL-1 beta-dependent inflammation and the stimulation of epithelial cells to produce TNF-alpha. Gal-10 crystals show susceptibility to pH changes and charged residue substitutions at the protein packing interfaces, manifesting the role of charge-charge attractions across protein-protein interaction interfaces in governing gal-10 crystallization. To dissolve the gal-10 crystal, the ionic peptides R9 and R12Y8 were identified to eliminate the interprotein charge-charge interactions. The efficacy of R12Y8 in mitigating the gal-10 crystallopathy in vivo was assessed in a crystal-induced lung inflammation mice model. The mice intratracheally administrated by R12Y8 exhibited a downregulated release of proinflammatory cytokines and reduced infiltration of inflammatory cells in the lungs. Our study demonstrates that the pathogenic gal-10 crystallization is readily eliminated by R-rich peptides, which may display translational potentials for the treatment of gal-10 crystallopathy.

引用

页码：8949 / 8961

页数：13