Ma Ya, Tong Xiaoling, Huang Yamei, Zhou Xin, Yang Chunhua, Chen Jiucun, Dai Fangyin, Xiao Bo
Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, 100 Piedmont Avenue SE, Atlanta, Georgia 30302, United States.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):6231-6242. doi: 10.1021/acsbiomaterials.9b00862. Epub 2019 Oct 17.
Silk sericin (SS) is abundant in silk industry wastewater, and it has emerged as a promising natural protein for biomedical research. However, its therapeutic potential against ulcerative colitis (UC) has not been exploited. The objective of this study is to investigate the therapeutic effects of SS in a dextran sulfate sodium-induced UC mouse model, and further discover its underlying mechanisms. The purified SS molecules showed negative cytotoxicity, and could be efficiently internalized by colonic epithelial cells and macrophages. In vitro experiments revealed that it could accelerate the mucosal healing, down-regulate the production of pro-inflammatory factors, increase the secretion of anti-inflammatory cytokines, and eliminate the intracellular reactive oxygen species. Finally, animal experiments confirmed that oral administration of hydrogel (chitosan/alginate)-embedding SS molecules attenuated UC-induced symptoms (e.g., body weight loss, colon shortening, increase of spleen weight, and histopathological appearance), which was supported by signs of mucosal healing, anti-inflammation, and elevation of the amounts of tight junction proteins (occludin and zonula occludens-1) and mucin protein (MUC2). Taken together, our results demonstrate that SS can be exploited as a promising oral natural therapeutic for UC treatment with the aid of hydrogel.
丝胶蛋白(SS)在丝绸工业废水中含量丰富,已成为生物医学研究中一种有前景的天然蛋白质。然而,其对溃疡性结肠炎(UC)的治疗潜力尚未得到开发。本研究的目的是研究SS在葡聚糖硫酸钠诱导的UC小鼠模型中的治疗效果,并进一步发现其潜在机制。纯化的SS分子显示出负细胞毒性,并且可以被结肠上皮细胞和巨噬细胞有效内化。体外实验表明,它可以加速黏膜愈合,下调促炎因子的产生,增加抗炎细胞因子的分泌,并消除细胞内活性氧。最后,动物实验证实,口服嵌入水凝胶(壳聚糖/海藻酸盐)的SS分子可减轻UC诱导的症状(如体重减轻、结肠缩短、脾脏重量增加和组织病理学表现),黏膜愈合、抗炎以及紧密连接蛋白(闭合蛋白和紧密连接蛋白-1)和黏蛋白(MUC2)含量升高的迹象也支持了这一点。综上所述,我们的结果表明,借助水凝胶,SS可作为一种有前景的口服天然疗法用于UC治疗。