Hwang Dae Yeon, Kim Suna, Hong Hyun Sook
1Department of Medicine, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea.
2Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104 Republic of Korea.
Tissue Eng Regen Med. 2017 Oct 13;15(1):63-73. doi: 10.1007/s13770-017-0085-7. eCollection 2018 Feb.
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.
肠道炎症会改变黏膜中的免疫反应并破坏结肠结构，从而导致诸如炎症性肠病等严重疾病。因此，调节炎症性肠病中的肠道完整性和免疫反应可能是减轻损害严重程度需考虑的关键因素。P物质（SP）是一种参与细胞增殖、迁移和免疫调节的内源性肽，可对包括角膜损伤、类风湿性关节炎和糖尿病并发症在内的多种疾病发挥治疗作用。研究发现SP可提高连接分子的表达。鉴于此前报道的SP的功能，推测SP能够通过控制肠道结构以及免疫反应，对肠道疾病发挥有益作用。在本研究中，我们通过注射SP来探究其对葡聚糖硫酸钠诱导的肠道损伤的治疗效果。通过分析隐窝结构、增殖细胞池和免疫细胞浸润来评估SP的作用。葡聚糖硫酸钠处理引发了异常免疫反应并破坏了肠道上皮屏障。然而，SP联合处理通过减轻炎症反应并使肠道结构保持更完整，明显阻止了肠道损伤的发展。对慢性损伤给予SP处理也通过保持结肠组织的完整性促进了肠道再生。此外，SP处理明显抑制了葡聚糖硫酸钠诱导的上皮连接分子的减少。综上所述，我们的数据表明SP可能通过调节屏障结构和免疫反应来减轻肠道损伤。我们的结果表明SP可作为肠道损伤的候选治疗药物。
