Protective effects of transforming growth factor β2 in intestinal epithelial cells by regulation of proteins associated with stress and endotoxin responses.
Protective effects of transforming growth factor β2 in intestinal epithelial cells by regulation of proteins associated with stress and endotoxin responses.
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DOI：
10.1371/journal.pone.0117608
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chatterton DE
中科院分区：
文献类型：
--
作者：
Nguyen DN;Jiang P;Jacobsen S;Sangild PT;Bendixen E;Chatterton DE
转化生长因子（Transforming growth factor，TGF）-β2是乳和初乳中重要的抗炎蛋白。TGF-β2补充剂似乎可以减少生命早期的肠道炎性疾病，如幼龄小鼠的坏死性小肠结肠炎（NEC）。然而，TGF-β2保护未成熟肠上皮细胞（IEC）的分子机制仍有待进一步阐明，然后才能考虑对婴儿进行干预。用TGF-β2和/或脂多糖（LPS）处理猪IEC PsIc 1，随后使用二维凝胶电泳-MS和基于LC-MS的蛋白质组学分析细胞蛋白质组的变化。TGF-β2单独诱导13种蛋白质的差异表达，并且大多数鉴定的蛋白质与应激反应、TGF-β和Toll样受体4信号级联相关。特别是，一系列的热休克蛋白有类似的差异趋势，如以前所示，在肠的NEC抗性早产猪和年轻的小鼠。此外，基于LC-MS的蛋白质组学和Western印迹分析显示，在LPS攻击的IEC中，用TGF-β2处理后有20种差异表达的蛋白质。其中13个蛋白与应激反应通路相关，其中5个蛋白在LPS刺激后改变，TGF-β2可使其恢复，而6个蛋白仅在LPS刺激后的IEC中表达差异。基于先前报道的生物学功能，这些模式表明TGF-β2在IEC中的抗应激和抗炎作用。我们的结论是，饮食或内源性来源的TGF-β2可以调节IEC对LPS刺激的反应，从而支持细胞内稳态和先天免疫对细菌定植的反应，以及生命早期的第一次肠道喂养。
Transforming growth factor (TGF)-β2 is an important anti-inflammatory protein in milk and colostrum. TGF-β2 supplementation appears to reduce gut inflammatory diseases in early life, such as necrotizing enterocolitis (NEC) in young mice. However, the molecular mechanisms by which TGF-β2 protects immature intestinal epithelial cells (IECs) remain to be more clearly elucidated before interventions in infants can be considered. Porcine IECs PsIc1 were treated with TGF-β2 and/or lipopolysaccharide (LPS), and changes in the cellular proteome were subsequently analyzed using two-dimensional gel electrophoresis-MS and LC-MS-based proteomics. TGF-β2 alone induced the differential expression of 13 proteins and the majority of the identified proteins were associated with stress responses, TGF-β and Toll-like receptor 4 signaling cascades. In particular, a series of heat shock proteins had similar differential trends as previously shown in the intestine of NEC-resistant preterm pigs and young mice. Furthermore, LC-MS-based proteomics and Western blot analyses revealed 20 differentially expressed proteins following treatment with TGF-β2 in LPS-challenged IECs. Thirteen of these proteins were associated with stress response pathways, among which five proteins were altered by LPS and restored by TGF-β2, whereas six were differentially expressed only by TGF-β2 in LPS-challenged IECs. Based on previously reported biological functions, these patterns indicate the anti-stress and anti-inflammatory effects of TGF-β2 in IECs. We conclude that TGF-β2 of dietary or endogenous origin may regulate the IEC responses against LPS stimuli, thereby supporting cellular homeostasis and innate immunity in response to bacterial colonization, and the first enteral feeding in early life.
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影响因子：
3.3
作者：
Chen, Songhai;Lin, Fang;Hamm, Heidi E.
通讯作者：
Hamm, Heidi E.
线虫性小肠结肠炎发病机理中的先天免疫信号传导。
影响因子：
--
作者：
Hackam DJ;Afrazi A;Good M;Sodhi CP
通讯作者：
Sodhi CP
DOI：
10.1152/ajpgi.00141.2001
发表时间：
2002-05-01
影响因子：
4.5
作者：
Bitar, KN
通讯作者：
Bitar, KN
影响因子：
3.6
作者：
Jiang, Pingping;Smith, Birgitte;Sangild, Per Torp
通讯作者：
Sangild, Per Torp
影响因子：
4.2
作者：
Jiang, Pingping;Siggers, Jayda Lee Ann;Wan, Jennifer Man-Fan
通讯作者：
Wan, Jennifer Man-Fan