Suppr超能文献

几丁质酶和几丁质酶样蛋白作为炎症性疾病的治疗靶点,特别关注炎症性肠病。

Chitinases and Chitinase-Like Proteins as Therapeutic Targets in Inflammatory Diseases, with a Special Focus on Inflammatory Bowel Diseases.

机构信息

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

OncoArendi Therapeutics SA, 02-089 Warsaw, Poland.

出版信息

Int J Mol Sci. 2021 Jun 28;22(13):6966. doi: 10.3390/ijms22136966.

Abstract

Chitinases belong to the evolutionarily conserved glycosyl hydrolase family 18 (GH18). They catalyze degradation of chitin to -acetylglucosamine by hydrolysis of the β-(1-4)-glycosidic bonds. Although mammals do not synthesize chitin, they possess two enzymatically active chitinases, i.e., chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase), as well as several chitinase-like proteins (YKL-40, YKL-39, oviductin, and stabilin-interacting protein). The latter lack enzymatic activity but still display oligosaccharides-binding ability. The physiologic functions of chitinases are still unclear, but they have been shown to be involved in the pathogenesis of various human fibrotic and inflammatory disorders, particularly those of the lung (idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, sarcoidosis, and asthma) and the gastrointestinal tract (inflammatory bowel diseases (IBDs) and colon cancer). In this review, we summarize the current knowledge about chitinases, particularly in IBDs, and demonstrate that chitinases can serve as prognostic biomarkers of disease progression. Moreover, we suggest that the inhibition of chitinase activity may be considered as a novel therapeutic strategy for the treatment of IBDs.

摘要

几丁质酶属于进化上保守的糖苷水解酶家族 18(GH18)。它们通过水解β-(1-4)糖苷键催化几丁质降解为β-N-乙酰氨基葡萄糖。尽管哺乳动物不合成几丁质,但它们具有两种具有酶活性的几丁质酶,即几丁三糖酶(CHIT1)和酸性哺乳动物几丁质酶(AMCase),以及几种几丁质酶样蛋白(YKL-40、YKL-39、输卵管蛋白和稳定素相互作用蛋白)。后者缺乏酶活性,但仍具有寡糖结合能力。几丁质酶的生理功能尚不清楚,但已表明它们参与了各种人类纤维化和炎症性疾病的发病机制,特别是肺部(特发性肺纤维化、慢性阻塞性肺疾病、结节病和哮喘)和胃肠道(炎症性肠病(IBD)和结肠癌)。在这篇综述中,我们总结了目前关于几丁质酶的知识,特别是在 IBD 中的知识,并证明几丁质酶可以作为疾病进展的预后生物标志物。此外,我们建议抑制几丁质酶活性可以被考虑作为治疗 IBD 的一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb98/8268069/0137d6854f83/ijms-22-06966-g001.jpg

相似文献

2
Chitinases and Chitinase-Like Proteins in Obstructive Lung Diseases - Current Concepts and Potential Applications.
Int J Chron Obstruct Pulmon Dis. 2020 Apr 23;15:885-899. doi: 10.2147/COPD.S236640. eCollection 2020.
4
Chitinases: Therapeutic Scaffolds for Allergy and Inflammation.
Recent Pat Inflamm Allergy Drug Discov. 2020;14(1):46-57. doi: 10.2174/1872213X14666200114184054.
5
The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.
Mol Cell Pediatr. 2015 Dec;2(1):3. doi: 10.1186/s40348-015-0014-6. Epub 2015 Feb 27.
6
Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury.
Annu Rev Physiol. 2011;73:479-501. doi: 10.1146/annurev-physiol-012110-142250.
7
Direct comparison of chitinolytic properties and determination of combinatory effects of mouse chitotriosidase and acidic mammalian chitinase.
Int J Biol Macromol. 2019 Aug 1;134:882-890. doi: 10.1016/j.ijbiomac.2019.05.097. Epub 2019 May 17.
8
Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease.
World J Gastroenterol. 2014 Feb 7;20(5):1127-38. doi: 10.3748/wjg.v20.i5.1127.
9
Chitinases and chitinase-like proteins in asthma.
Semin Immunol. 2023 May;67:101759. doi: 10.1016/j.smim.2023.101759. Epub 2023 Apr 7.
10
Human Chitinases: Structure, Function, and Inhibitor Discovery.
Adv Exp Med Biol. 2019;1142:221-251. doi: 10.1007/978-981-13-7318-3_11.

引用本文的文献

1
Application of Biomarkers in Spinal Muscular Atrophy.
Int J Mol Sci. 2025 Jul 17;26(14):6887. doi: 10.3390/ijms26146887.
2
Chitinase-1 inhibition attenuates metabolic dysregulation and restores homeostasis in MASH animal models.
Front Immunol. 2025 May 29;16:1544973. doi: 10.3389/fimmu.2025.1544973. eCollection 2025.
6
Insights into spinal muscular atrophy from molecular biomarkers.
Neural Regen Res. 2025 Jul 1;20(7):1849-1863. doi: 10.4103/NRR.NRR-D-24-00067. Epub 2024 Jun 26.
8
Edible bird's nest alleviates pneumonia caused by tobacco smoke inhalation through the TNFR1/NF-κB/NLRP3 pathway.
Food Sci Nutr. 2024 Apr 1;12(6):4196-4210. doi: 10.1002/fsn3.4080. eCollection 2024 Jun.

本文引用的文献

1
Discovery of , a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis.
J Med Chem. 2020 Dec 24;63(24):15527-15540. doi: 10.1021/acs.jmedchem.0c01179. Epub 2020 Oct 20.
3
Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase.
ACS Med Chem Lett. 2020 Apr 24;11(6):1228-1235. doi: 10.1021/acsmedchemlett.0c00092. eCollection 2020 Jun 11.
4
A Series of Compounds Bearing a Dipyrido-Pyrimidine Scaffold Acting as Novel Human and Insect Pest Chitinase Inhibitors.
J Med Chem. 2020 Feb 13;63(3):987-1001. doi: 10.1021/acs.jmedchem.9b01154. Epub 2020 Feb 3.
5
Development of Dual Chitinase Inhibitors as Potential New Treatment for Respiratory System Diseases.
J Med Chem. 2019 Aug 8;62(15):7126-7145. doi: 10.1021/acs.jmedchem.9b00681. Epub 2019 Jul 23.
6
Human Chitinases: Structure, Function, and Inhibitor Discovery.
Adv Exp Med Biol. 2019;1142:221-251. doi: 10.1007/978-981-13-7318-3_11.
7
Chitin in Arthropods: Biosynthesis, Modification, and Metabolism.
Adv Exp Med Biol. 2019;1142:169-207. doi: 10.1007/978-981-13-7318-3_9.
8
Bacterial Chitinase System as a Model of Chitin Biodegradation.
Adv Exp Med Biol. 2019;1142:131-151. doi: 10.1007/978-981-13-7318-3_7.
9
Identification of Chitinase-3-Like Protein 1 as a Novel Neutrophil Antigenic Target in Crohn's Disease.
J Crohns Colitis. 2019 Jul 25;13(7):894-904. doi: 10.1093/ecco-jcc/jjz012.
10
Chitin, chitinases, and chitin lectins: Emerging roles in human pathophysiology.
Pathophysiology. 2018 Dec;25(4):253-262. doi: 10.1016/j.pathophys.2018.02.005. Epub 2018 Mar 6.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验