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Purified PEGylated porcine glucagon-like peptide-2 reduces the severity of colonic injury in a murine model of experimental colitis

文献类型： 外文期刊

作者： Qi, Ke-ke 1 ; Wu, Jie 1 ; Wan, Jing 1 ; Men, Xiao-ming 1 ; Xu, Zi-wei 1 ;

作者机构： 1.Zhejiang Acad Agr Sci, Inst Anim Sci, Hangzhou 310021, Zhejiang, Peoples R China

关键词： Colitis;Dextran sulfate sodium;Ion-exchange chromatography;PEGylation;Porcine glucagon-like peptide-2

期刊名称：PEPTIDES （ 影响因子：3.75； 五年影响因子：3.389 ）

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收录情况： SCI

摘要： The rapid degradation of porcine glucagon-like peptide-2 (pGLP-2) by the enzyme dipeptidyl peptidase-IV (DPP-IV) is the main impediment in the development of pGLP-2 as a potential therapeutic agent for intestinal dysfunction and damage. In this study, one mono-modified Lys30- polyethylene glycol (PEG)-pGLP-2 was prepared using mPEG-succinimidyl propionate. To determine the optimized condition for PEGylation, the reactions were monitored by RP-HPLC and MALDI-TOF-MS. Stability was tested in purified DPP-IV in vitro. In vivo, the protective effects for colonic injury were measured in dextran sulfate sodium (DSS)-induced colitis in mice. The monoPEGylated products reached the maximum yield at 4:1 ratio of mPEG 5k-SPA to pGLP-2. An effective method of successfully separating PEGylated pGLP-2 from mPEG-SPA5kD using CM Sepharose Fast Flow resin was established. The half-life of Lys30-PEG-pGLP-2 was 16-fold longer than that of pGLP-2 in DPP-IV. The DSS mice exhibited marked weight loss), which was significantly reduced by Lys30-PEG-pGLP-2 therapy. DSS treatment significantly increased colonic damage score, which was significantly reduced by administration of Lys30-PEG-pGLP-2 in DSS-mice. DSS-induced colitis clearly induced Myeloperoxidase activity in the colon, which was significantly reduced by treatments with 3% DSS-pGLP-2 or 3% DSS-PEG-pGLP-2. These results showed that site-specific Lys30-PEG- GLP-2 was resistant to degradation and reduced the severity of colonic injury in murine colitis. The enhanced biological potency of this product highlighted its potential as a therapeutic agent for intestinal diseases.

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[1]Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats. Qi, Ke-ke,Lv, Jia-jia,Wu, Jie,Xu, Zi-wei. 2017

[2]Porcine glucagon-like peptide-2 microspheres ameliorate inflammation in lipopolysaccharide-challenged weaning piglets. Wu, J.,Qi, K. K.,Xu, Z. W..

[3]Effect of porcine glucagon-like peptides-2 on tight junction in GLP-2R+IPEC-J2 cell through the PI(3)k/Akt/mTOR/p70(S6K) signalling pathway. Qi, K. K.,Sun, Y. Q.,Wan, J.,Deng, B.,Men, X. M.,Wu, J.,Xu, Z. W..

[4]PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS. Qi, K. K.,Wu, J.,Deng, B.,Li, Y. M.,Xu, Z. W..

[5]Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide. Qi, Ke-ke,Wu, Jie,Xu, Zi-wei.

[6]Recombinant Lactococcus lactis expressing porcine insulin-like growth factor I ameliorates DSS-induced colitis in mice. Liu, Shujie,Li, Yongming,Deng, Bo,Xu, Ziwei. 2016

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