Recombinant protein Schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis.
Recombinant protein Schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis.
复制标题
重组蛋白日本血吸虫衍生分子通过抑制 miRNA-217-5p 减轻细胞凋亡来减轻葡聚糖硫酸钠诱导的结肠炎
DOI：
10.3748/wjg.v27.i46.7982
复制
发表时间：
2021-12-14
影响因子：
4.3
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Zhang LC;Wu XY;Yang RB;Chen F;Liu JH;Hu YY;Wu ZD;Wang LF;Sun X
炎症性肠病（IBD）影响着全世界数百万人，并且在工业化国家已经成为一个日益严重的问题。治疗靶点的缺乏限制了IBD的治疗。研究发现，寄生线虫感染可以改善临床和实验性结肠炎。本课题组前期研究发现，日本血吸虫大肠杆菌分泌的16-kDa蛋白rSj 16对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎具有保护作用。细胞凋亡是结肠炎发病机制中的重要因素。然而，目前尚不清楚rSj 16对结肠炎的作用是否与细胞凋亡有关。目的探讨重组Sj 16对结肠炎的保护作用是否与细胞凋亡有关及其机制。方法采用DSS诱导大鼠结肠炎模型。评估结肠炎的严重程度。WB法检测结肠组织中糖代谢相关基因的变化。Q-PCR检测miRNA-217- 5 p和HNF 1B的变化。在体外培养条件下，WB法检测肠上皮细胞凋亡相关基因的变化。TUNEL染色和流式细胞术检测细胞凋亡。结果rSj 16对DSS诱导的结肠炎小鼠的临床活性有明显的抑制作用。TUNEL染色和WB结果显示，DSS处理后结肠组织中细胞凋亡增加，rSj 16处理后结肠组织中细胞凋亡明显减少。与正常小鼠相比，DSS诱导的结肠炎小鼠结肠组织中miR-217- 5 p的表达增加。此外，DSS给药后，miR-217- 5 p靶基因hnf 1b降低。与DSS组相比，rSj 16处理后miR-217- 5 p表达降低，HNF 1B表达升高。与单纯足叶乙甙处理相比，足叶乙甙与miR-217- 5 p模拟物联合处理MODE-K细胞后，裂解型Caspase-3和Bax表达增加，Bcl-2表达降低，HNF 1B表达显著降低，提示miR-217- 5 p在结肠上皮细胞中起促凋亡作用，下调靶基因hnf 1b。MODE-K细胞经rSj 16处理后，miR-217- 5 p表达显著降低，HNF 1B表达增加，细胞凋亡减少。结论rSj 16对IBD的保护作用可能与细胞凋亡有关，miRNA-217- 5 p可能成为IBD治疗的新靶点。
BACKGROUND Inflammatory bowel disease (IBD) affects millions of people worldwide and has emerged as a growing problem in industrialized nations. The lack of therapeutic targets has limited the treatment of IBD. Studies found that parasitic nematode infections can ameliorate clinical and experimental colitis. Our previous study found that rSj16, a 16-kDa secreted protein of Schistosoma japonicum produced by Escherichia coli, has protective effects on dextran sulfate sodium (DSS)-induced colitis in mice. Apoptosis is an important factor in the pathogenesis of colitis. However, it is not clear whether the effect of rSj16 on colitis is related to apoptosis. AIM To investigate whether the protective effects of rSj16 on colitis is related to apoptosis and its mechanism. METHODS In-vivo , colitis was induced by DSS. The severity of colitis was assessed. WB was used to detect the changes of apoptosis-related genes in colon tissues. Q-PCR was used to detect the changes of miRNA-217-5p and HNF1B. In-vitro, WB was used to detect the changes of apoptosis-related genes in intestinal epithelial cells. TUNNEL staining and flow cytometry were used to detect cell apoptosis. RESULTS rSj16 attenuates clinical activity in DSS-induced colitis mice. TUNNEL staining and WB results showed that apoptosis was increased in colon tissue after treatment with DSS, and the apoptosis of colon tissue was significantly reduced after treatment with rSj16. Compared with normal mice, the expression of miR-217-5p was increased in colon tissue of DSS-induced colitis mice. In addition, the miR-217-5p target gene hnf1b was decreased after administration of DSS. After treatment with rSj16, the expression of miR-217-5p was decreased and the expression of HNF1B was increased compared with the DSS-treated group. When Etoposide was used in combination with miR-217-5p mimic on MODE-K cells, the expression of cleaved-Caspase-3 and Bax was increased, and Bcl-2 was decreased compared with only Etoposide treatment, the expression of HNF1B was significantly reduced, suggesting that miR-217-5p acts as a pro-apoptotic in colon epithelial cells and down-regulates the target gene hnf1b. After rSj16 administration in MODE-K cells, miR-217-5p expression was significantly decreased, HNF1B expression was increased, and apoptosis was reduced. CONCLUSION The protective effects of rSj16 on colitis is related to apoptosis and miRNA-217-5p may be a further target for therapeutic intervention against IBD.
登录
查看更多内容
miR-665的上调通过抑制内质网应激成分XBP1和ORMDL3促进炎症性肠病中的细胞凋亡和结肠炎
影响因子：
9
作者：
Li M;Zhang S;Qiu Y;He Y;Chen B;Mao R;Cui Y;Zeng Z;Chen M
通讯作者：
Chen M
影响因子：
4.6
作者：
De Vas, Matias G.;Kopp, Janel L.;Haumaitre, Cecile
通讯作者：
Haumaitre, Cecile
影响因子：
5.6
作者：
Moon, Dong-Oh;Park, Sung-Yong;Kim, Gi-Young
通讯作者：
Kim, Gi-Young
Raf 激酶抑制剂蛋白介导肠上皮细胞凋亡并促进人类和小鼠的 IBD。
影响因子：
24.5
作者：
Lin, Wenlong;Ma, Chunmei;Wang, Xiaojian
通讯作者：
Wang, Xiaojian
影响因子：
5.1
作者：
Qi, Yujuan;Zhang, Kai;Wu, Zhenhua
通讯作者：
Wu, Zhenhua