Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4.
Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4.
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DOI：
10.1371/journal.pone.0038798
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Renes IB
中科院分区：
文献类型：
--
作者：
Burger-van Paassen N;Loonen LM;Witte-Bouma J;Korteland-van Male AM;de Bruijn AC;van der Sluis M;Lu P;Van Goudoever JB;Wells JM;Dekker J;Van Seuningen I;Renes IB
粘蛋白Muc 2是肠粘液层的结构组分。Muc 2的缺乏导致该层的损失，从而允许直接的细菌-上皮相互作用。我们假设，粘液层的缺乏导致先天防御肽的表达增加。具体而言，我们旨在研究Muc 2缺乏（Muc 2 −/−）对断奶前后不久肠道中再生胰岛衍生蛋白3 β（Reg 3 β）、再生胰岛衍生蛋白3 γ（Reg 3 γ）和血管生成素-4（Ang 4）表达的影响。在出生后第14天（P14，即断奶前）和P28（即断奶后）收集Muc 2 −/−和野生型（WT）小鼠的肠组织。通过实时定量PCR、Western印迹、原位杂交和免疫组化研究Reg 3 β、Reg 3 γ和Ang 4的表达。Reg 3 β和Reg 3 γ由不同的上皮细胞类型表达;即肠上皮细胞、潘氏细胞和杯状细胞。此外，Ang 4表达仅限于潘氏细胞和杯状细胞。在断奶前后，WT和Muc 2 −/−小鼠的Reg 3 β、Reg 3 γ和Ang 4表达不同。有趣的是，Muc 2的缺乏强烈增加了小肠和结肠中的Reg 3 β和Reg 3 γ表达。最后，仅在P28时Muc 2 −/−小鼠的远端结肠中观察到结肠炎的形态学体征，此时Reg 3 β、Reg 3 γ和Ang 4的表达水平最低。杯状细胞表达Reg 3蛋白和Ang 4表明杯状细胞在先天防御中起重要作用。Muc 2缺失导致Reg 3 β和Reg 3 γ表达上调，表明Muc 2 −/−小鼠中细菌-上皮信号传导和先天防御反应发生改变。结肠炎发展与Reg 3 β、Reg 3 γ和Ang 4表达水平之间的负相关性可能指向这些先天防御肽在调节肠道炎症中的作用。
Mucin Muc2 is the structural component of the intestinal mucus layer. Absence of Muc2 leads to loss of this layer allowing direct bacterial-epithelial interactions. We hypothesized that absence of the mucus layer leads to increased expression of innate defense peptides. Specifically, we aimed to study the consequence of Muc2 deficiency (Muc2−/−) on the expression of regenerating islet-derived protein 3 beta (Reg3β), regenerating islet-derived protein 3 gamma (Reg3γ), and angiogenin-4 (Ang4) in the intestine shortly before and after weaning. Intestinal tissues of Muc2−/− and wild-type (WT) mice were collected at postnatal day 14 (P14, i.e. pre-weaning) and P28 (i.e. post-weaning). Reg3β, Reg3γ, and Ang4 expression was studied by quantitative real-time PCR, Western-blot, in situ hybridization, and immunohistochemistry. Reg3β and Reg3γ were expressed by diverging epithelial cell types; namely enterocytes, Paneth cells, and goblet cells. Additionally, Ang4 expression was confined to Paneth cells and goblet cells. Expression of Reg3β, Reg3γ, and Ang4 differed between WT and Muc2−/− mice before and after weaning. Interestingly, absence of Muc2 strongly increased Reg3β and Reg3γ expression in the small intestine and colon. Finally, morphological signs of colitis were only observed in the distal colon of Muc2−/− mice at P28, where and when expression levels of Reg3β, Reg3γ, and Ang4 were the lowest. Expression of Reg3 proteins and Ang4 by goblet cells point to an important role for goblet cells in innate defense. Absence of Muc2 results in up-regulation of Reg3β and Reg3γ expression, suggesting altered bacterial-epithelial signaling and an innate defense response in Muc2−/− mice. The inverse correlation between colitis development and Reg3β, Reg3γ, and Ang4 expression levels might point toward a role for these innate defense peptides in regulating intestinal inflammation.
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影响因子：
9.8
作者：
Sonnenburg JL;Chen CT;Gordon JI
通讯作者：
Gordon JI
影响因子：
4.9
作者：
Lepage, P;Seksik, P;Doré, J
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Doré, J
影响因子：
4.4
作者：
LeBouder, E;Rey-Nores, JE;Labéta, MO
通讯作者：
Labéta, MO
DOI：
10.1152/ajpgi.2001.280.5.g922
发表时间：
2001-05-01
影响因子：
4.5
作者：
Atuma, C;Strugala, V;Holm, L
通讯作者：
Holm, L
DOI：
10.1084/jem.191.10.1807
发表时间：
2000-05-15
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Labéta MO;Vidal K;Nores JE;Arias M;Vita N;Morgan BP;Guillemot JC;Loyaux D;Ferrara P;Schmid D;Affolter M;Borysiewicz LK;Donnet-Hughes A;Schiffrin EJ
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Schiffrin EJ