Age-Related Mucus Barrier Dysfunction in Mice Is Related to the Changes in Muc2 Mucin in the Colon.
Age-Related Mucus Barrier Dysfunction in Mice Is Related to the Changes in Muc2 Mucin in the Colon.
复制标题
DOI：
10.3390/nu15081830
复制
发表时间：
2023-04-11
期刊：
影响因子：
5.9
通讯作者：
Ren F
中科院分区：
文献类型：
--
作者：
Sang X;Wang Q;Ning Y;Wang H;Zhang R;Li Y;Fang B;Lv C;Zhang Y;Wang X;Ren F
在衰老过程中，粘液屏障的保护功能明显减弱，其中结肠粘液屏障功能的变化最受关注。此外，与结肠相关的疾病在成年后发病率显著增加，对老年人的健康构成威胁。然而，随着年龄的增长，结肠粘液屏障的具体变化及其可能的机制还没有完全阐明。为了了解衰老对结肠粘液屏障的影响，对2、12、18和24个月大的小鼠的结肠粘液层的变化进行了评估。用原位杂交荧光染色、AB/PAS染色和冷冻扫描电子显微镜分析了不同月龄小鼠结肠粘液的微生物侵入、厚度和结构。结果表明，老年结肠表现为肠粘液屏障功能障碍和粘液性质改变。在老化过程中，微生物侵入粘液层到达上皮细胞。与青年组比较，老龄组小鼠结肠粘液层厚度增加11.66μm，主要成分含量和糖化结构发生改变。其中，老年小鼠杯状细胞比例明显降低，调控杯状细胞分化的SPDEF基因表达减少。此外，参与粘蛋白核心结构形成和多糖修饰的关键酶的表达也随着年龄的变化而变化。形成核心结构的关键酶核心1β1，3-半乳糖基转移酶(C1GalT1)的表达增加1倍，核心2β1，6-乙酰氨基葡萄糖转移酶(C2GnT)和核心3-β1，3-乙酰氨基葡萄糖转移酶(C3GnT)的表达分别下降2-6倍和2倍。此外，粘蛋白-葡聚糖修饰酶之一唾液酸基转移酶的表达也减少了1倍。总之，我们的结果表明杯状细胞/糖基转移酶/O-葡聚糖轴在维持结肠粘液的物理化学性质和肠道环境的稳定中起着重要作用。
During aging, the protective function of mucus barrier is significantly reduced among which changes in colonic mucus barrier function received the most attention. Additionally, the incidence of colon-related diseases increases significantly in adulthood, posing a threat to the health of the elderly. However, the specific changes in colonic mucus barrier with aging and the underlying mechanisms have not been fully elucidated. To understand the effects of aging on the colonic mucus barrier, changes in the colonic mucus layer were evaluated in mice aged 2, 12, 18, and 24 months. Microbial invasion, thickness, and structure of colonic mucus in mice at different months of age were analyzed by in situ hybridization fluorescence staining, AB/PAS staining, and cryo-scanning electron microscopy. Results showed that the aged colon exhibited intestinal mucus barrier dys-function and altered mucus properties. During aging, microorganisms invaded the mucus layer to reach epithelial cells. Compared with young mice, the thickness of mucus layer in aged mice in-creased by 11.66 μm. And the contents of the main components and glycosylation structure of colon changed. Among them, the proportion of goblet cells decreased significantly in older mice, and the expression of spdef genes that regulate goblet cell differentiation decreased. Further, the expression of key enzymes involved in mucin core structure formation and glycan modification also changed with aging. The expression of core 1 β1,3-galactosyltransferase (C1GalT1) which is the key enzyme forming the main core structure increased by one time, while core 2 β1,6 N-acetylglucosaminyltransferase (C2GnT) and core 3 β1,3 N-acetylglucosaminyltransferase (C3GnT) decreased 2 to 6- and 2-fold, respectively. Also, the expression of sialyltransferase, one of the mucin-glycan modifying enzymes, was decreased by 1-fold. Overall, our results indicate that the goblet cells/glycosyltransferase/O-glycan axis plays an important role in maintaining the physicochemical properties of colonic mucus and the stability of intestinal environment.
登录
查看更多内容
影响因子：
3.7
作者：
Elderman M;Sovran B;Hugenholtz F;Graversen K;Huijskes M;Houtsma E;Belzer C;Boekschoten M;de Vos P;Dekker J;Wells J;Faas M
通讯作者：
Faas M
DOI：
10.1038/nri.2016.88
发表时间：
2016-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Johansson ME;Hansson GC
通讯作者：
Hansson GC
影响因子：
9.2
作者：
Caldara, Marina;Friedlander, Ronn S.;Kavanaugh, Nicole L.;Aizenberg, Joanna;Foster, Kevin R.;Ribbeck, Katharina
通讯作者：
Ribbeck, Katharina
影响因子：
4.6
作者：
Kamphuis JBJ;Mercier-Bonin M;Eutamène H;Theodorou V
通讯作者：
Theodorou V
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael