Kim Suna, Hong Hyun Sook
Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University, Seochun-dong, Kiheung-ku, Yong In, 17104, Republic of Korea.
College of Medicine/ East-West Medical Research Institute, Kyung Hee University, 1 Hoegi-dong. Dongdaemun-gu, Seoul, 02447, Republic of Korea; Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Kyung Hee University, Seoul, 02447, Republic of Korea.
Peptides. 2021 Mar;137:170494. doi: 10.1016/j.peptides.2021.170494. Epub 2021 Jan 10.
Substance-P (SP) is a neuropeptide that modulates immune responses and accelerates tissue repair in critical inflammatory disease. Liver fibrosis and cirrhosis are the ultimate outcomes of almost all chronic liver diseases caused by viral infection, steatohepatitis, autoimmune, and cholestatic injury. Despite the development of new drugs, liver transplantation is still the only fundamental treatment; thus, new therapeutic approaches to mitigate liver fibrosis and chronic inflammation are constantly being needed. The aim of this study was to examine the effect of SP on liver damage due to cholestatic stress. To induce cholestatic injury, common bile duct ligation (CBDL) was attempted, followed by systemic application of SP. SP treatment increased IL-10 and decreased TNF-α in serum with increasing levels of circulating regulatory T cells (Tregs) from the early stage of CBDL. Moreover, SP decreased CBDL-induced TGF-β1 expression in the circulation. This could create anti-inflammatory/anti-fibrotic environment under CBDL, which might ameliorate the progression of liver fibrosis in CBDL. Histological and molecular analysis revealed that SP treatment reduced ductular reaction, hepatic damage, and apoptotic hepatocytes, accompanied by diminishing type I collagen and upregulating MMP-9. These studies found that SP is a promising therapeutic candidate for immune-related liver disease as well as cholestatic liver disease, by providing hepatic protective effects via immune suppression.
P物质（SP）是一种神经肽，可调节免疫反应并加速严重炎症性疾病中的组织修复。肝纤维化和肝硬化是由病毒感染、脂肪性肝炎、自身免疫和胆汁淤积性损伤引起的几乎所有慢性肝病的最终结局。尽管有新药问世，但肝移植仍然是唯一的根本治疗方法；因此，不断需要新的治疗方法来减轻肝纤维化和慢性炎症。本研究的目的是研究SP对胆汁淤积性应激所致肝损伤的影响。为诱导胆汁淤积性损伤，尝试进行胆总管结扎（CBDL），随后全身应用SP。从CBDL早期开始，随着循环调节性T细胞（Tregs）水平的升高，SP治疗可使血清中IL-10增加，TNF-α降低。此外，SP可降低循环中CBDL诱导的TGF-β1表达。这可能在CBDL情况下创造抗炎/抗纤维化环境，从而可能改善CBDL中肝纤维化的进展。组织学和分子分析显示，SP治疗可减少胆管反应、肝损伤和凋亡肝细胞，同时减少I型胶原并上调MMP-9。这些研究发现，SP通过免疫抑制提供肝脏保护作用，是免疫相关性肝病以及胆汁淤积性肝病的有前景的治疗候选物。
