Targeting the gut barrier: identification of a homing peptide sequence for delivery into the injured intestinal epithelial cell.
Targeting the gut barrier: identification of a homing peptide sequence for delivery into the injured intestinal epithelial cell.
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DOI：
10.1016/j.surg.2009.05.007
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发表时间：
2009-08
期刊：
影响因子：
3.8
通讯作者：
Coimbra, Raul
中科院分区：
文献类型：
--
作者：
Costantini, Todd W.;Putnam, James G.;Sawada, Ritsuko;Baird, Andrew;Loomis, William H.;Eliceiri, Brian P.;Bansal, Vishal;Coimbra, Raul
严重的损伤导致肠屏障功能障碍，这可能是导致严重发病率和死亡率的原因。我们推测，挖掘展示在噬菌体上的多肽文库将识别在损伤后结合并内化到肠上皮中的多肽序列。我们利用小鼠严重的全层烧伤作为严重创伤的模型。通过筛选1012个展示独特多肽序列的噬菌体，确定了候选多肽。体内评估是通过将靶向噬菌体注射到烧伤后远端回肠的一段腔内，然后使用定量聚合酶链式反应(PCR)、DNA测序和量子点(Qdots)结合的多肽的共聚焦显微镜来分析多肽序列的摄取。噬菌体筛选确定T18肽序列(LTHPQDSPPASA)是进行体内试验的最佳候选序列。与非靶向噬菌体相比，损伤后肠道细胞的聚合酶链式反应显示出更高水平的T18序列。共聚焦显微镜观察到Qdots结合的多肽序列在损伤后内化到肠粘膜。我们已经确定了一个以受损的肠上皮为靶点的多肽序列，并可能允许开发靶向治疗来减轻炎症或其他小肠病理状况。
Severe injury results in intestinal barrier dysfunction that may be responsible for significant morbidity and mortality. We postulated that mining a peptide library that was displayed on phage would identify peptide sequences that bind and internalize into the gut epithelium following injury. We utilized a severe full thickness burn in mice as a model of severe injury. Candidate peptides were identified by screening 1012 phage displaying unique peptide sequences. In vivo assessment was performed by injecting targeted phage into the lumen of a segment of distal ileum following burn injury, then analyzed for uptake of peptide sequence using quantitative polymerase chain reaction (PCR), DNA sequencing, and confocal microscopy of the peptide bound to quantum dots (Qdots). Phage screening identified the peptide sequence T18 (LTHPQDSPPASA) as an optimal candidate for in vivo testing. PCR of intestinal cells following injury showed a higher level of T18 sequence when compared to untargeted phage. Confocal microscopy of the peptide sequence bound to Qdots showed internalization into gut mucosa following injury. We have identified a peptide sequence that targets the injured intestinal epithelium and may allow for the development of targeted therapies to attenuate inflammation, or other pathologic conditions of the small bowel.
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影响因子：
3.8
作者：
Deitch, EA
通讯作者：
Deitch, EA
影响因子：
29.4
作者：
Schwarz, Brad T.;Wang, Fengjun;Turner, Jerrold R.
通讯作者：
Turner, Jerrold R.
影响因子：
4.8
作者：
Nishimura, Shinpei;Takahashi, Shunsuke;Kuniyasu, Akihiko
通讯作者：
Kuniyasu, Akihiko
影响因子：
4.4
作者：
Leaphart, Cynthia L.;Cavallo, Jaime;Hackam, David J.
通讯作者：
Hackam, David J.
DOI：
10.1152/ajpgi.00090.2006
发表时间：
2006-11-01
影响因子：
4.5
作者：
Clark, Jessica A.;Doelle, Sarah M.;Dvorak, Bohuslav
通讯作者：
Dvorak, Bohuslav