DataVXACS Applied Materials & InterfacesPaper
journal article·2025-02-12

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

Wenbo Zhang, Shuyuan Li, Yang Wang, Shuli Liu, Lei Liu, Zhun Deng, Shanshan Mo, Mingrui Chen, Zhenyan Li, Ruonan Wang, Xin Zhou, Longxin Xu, Lanlan Yu, Zhenlin Liu, Hongwei Li, Junbo Liang, Chenxuan Wang

ACS Applied Materials & Interfaces· Volume 17· Issue 6
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Source abstract

Abstract

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-1β-dependent inflammation and the stimulation of epithelial cells to produce TNF-α. 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.
Source: openalex_inverted_index · Quality: baseline

Research context

Materials processing

OpenAlex topics: Galectins and Cancer Biology · Alkaline Phosphatase Research Studies · Macrophage Migration Inhibitory Factor

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences

School of Basic Medicine Peking Union Medical College

State Key Laboratory of Vascular Homeostasis and Remodeling, Institute of Cardiovascular Sciences, School of Basic Medical Sciences

Peking University Health Science Center

Department of Clinical Laboratory

Peking University Civil Aviation School of Clinical Medicine

Department of Cardiology, Boston Children’s Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, United States

Department of Pediatrics, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, United States

Department of Medical Engineering

Peking University Third Hospital

Beijing Nuclear Magnetic Resonance Center

Peking University

Center for Bioinformatics, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine

Peking Union Medical College

Funding

National Key Research and Development Program of China · Chinese Academy of Medical Sciences · Natural Science Foundation of Beijing Municipality · Fundamental Research Funds for the Central Universities · National Natural Science Foundation of China · State Key Laboratory Special Fund · Haihe Laboratory of Cell Ecosystem

References (50)

Show source-provided references
1. 10.1038/nrneph.2017.1010.1038/nrneph.2017.10 ↗
2. 10.1056/NEJMra160161110.1056/NEJMra1601611 ↗
3. 10.1038/nature0451610.1038/nature04516 ↗
4. 10.1172/JCI6367910.1172/JCI63679 ↗
5. 10.1038/ncomms1027410.1038/ncomms10274 ↗
6. 10.1097/RHU.0b013e31826149a210.1097/RHU.0b013e31826149a2 ↗
7. 10.1126/scitranslmed.aad610010.1126/scitranslmed.aad6100 ↗
8. 10.1016/j.coi.2021.03.01310.1016/j.coi.2021.03.013 ↗
9. 10.1007/s11882-019-0868-010.1007/s11882-019-0868-0 ↗
10. 10.4049/jimmunol.180010710.4049/jimmunol.1800107 ↗
11. 10.3390/molecules2311293110.3390/molecules23112931 ↗
12. 10.1017/s146239940800071910.1017/s1462399408000719 ↗
13. 10.1038/nri253610.1038/nri2536 ↗
14. 10.1067/mai.2000.10571210.1067/mai.2000.105712 ↗
15. 10.1126/science.aaw429510.1126/science.aaw4295 ↗
16. 10.1016/j.jaci.2019.08.02710.1016/j.jaci.2019.08.027 ↗
17. 10.2500/ajra.2015.29.423110.2500/ajra.2015.29.4231 ↗
18. 10.1002/alr.2221410.1002/alr.22214 ↗
19. 10.3390/pharmaceutics1003008310.3390/pharmaceutics10030083 ↗
20. 10.4314/tjpr.v16i3.2910.4314/tjpr.v16i3.29 ↗
21. 10.1016/S0969-2126(01)00275-110.1016/S0969-2126(01)00275-1 ↗
22. 10.1093/glycob/cwx10710.1093/glycob/cwx107 ↗
23. 10.1021/acs.chemrev.7b0030510.1021/acs.chemrev.7b00305 ↗
24. 10.3389/fneur.2020.0010810.3389/fneur.2020.00108 ↗
25. 10.1016/S0891-5849(01)00734-110.1016/S0891-5849(01)00734-1 ↗
26. 10.1006/jmbi.1998.184310.1006/jmbi.1998.1843 ↗
27. 10.1021/bi00507a03010.1021/bi00507a030 ↗
28. Vranken D. V. · 2012
29. 10.1021/acs.jproteome.8b0014810.1021/acs.jproteome.8b00148 ↗
30. 10.1021/mp300711710.1021/mp3007117 ↗
31. 10.1038/mt.2009.29710.1038/mt.2009.297 ↗
32. 10.1007/s12017-017-8441-210.1007/s12017-017-8441-2 ↗
33. 10.1002/0471140864.ps1925s7910.1002/0471140864.ps1925s79 ↗
34. Israelachvili J. N. · 2015
35. 10.1016/j.intimp.2023.11005410.1016/j.intimp.2023.110054 ↗
36. 10.1159/00052485510.1159/000524855 ↗
37. 10.1016/j.intimp.2024.11308110.1016/j.intimp.2024.113081 ↗
38. 10.1007/s00405-017-4717-210.1007/s00405-017-4717-2 ↗
39. 10.1038/nri253610.1038/nri2536 ↗
40. 10.33549/physiolres.93353110.33549/physiolres.933531 ↗
41. 10.1016/j.phrs.2006.01.00610.1016/j.phrs.2006.01.006 ↗
42. 10.1016/j.ejphar.2006.03.01110.1016/j.ejphar.2006.03.011 ↗
43. 10.1016/j.drudis.2023.10371410.1016/j.drudis.2023.103714 ↗
44. 10.1038/nrd.2016.2910.1038/nrd.2016.29 ↗
45. 10.1016/j.nantod.2018.10.00810.1016/j.nantod.2018.10.008 ↗
46. 10.1038/s41598-018-33766-410.1038/s41598-018-33766-4 ↗
47. 10.1074/jbc.M70097020010.1074/jbc.M700970200 ↗
48. 10.1021/acs.nanolett.1c0481710.1021/acs.nanolett.1c04817 ↗
49. 10.1021/acs.langmuir.0c0325510.1021/acs.langmuir.0c03255 ↗
50. 10.1021/acsami.2c0370710.1021/acsami.2c03707 ↗