Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.
OncoArendi Therapeutics SA, 02-089 Warsaw, Poland.
Int J Mol Sci. 2021 Jun 28;22(13):6966. doi: 10.3390/ijms22136966.
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.
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。