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Kim S, Hong HS. Substance-P prevents the cholestatic liver injury by regulating inflammatory responses. Peptides. 2021;137:170494doi: 10.1016/j.peptides.2021.170494.
Kim, S., & Hong, H. S. (2021). Substance-P prevents the cholestatic liver injury by regulating inflammatory responses. Peptides, 137170494. https://doi.org/10.1016/j.peptides.2021.170494
Kim, Suna, and Hong, Hyun Sook. "Substance-P prevents the cholestatic liver injury by regulating inflammatory responses." Peptides vol. 137 (2021): 170494. doi: https://doi.org/10.1016/j.peptides.2021.170494
Kim S, Hong HS. Substance-P prevents the cholestatic liver injury by regulating inflammatory responses. Peptides. 2021 Mar;137:170494. doi: 10.1016/j.peptides.2021.170494. Epub 2021 Jan 10. PMID: 33440226.
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Peptides. 2021 Mar;137:170494. doi: 10.1016/j.peptides.2021.170494. Epub 2021 Jan 10.

Substance-P prevents the cholestatic liver injury by regulating inflammatory responses.

Peptides

Suna Kim, Hyun Sook Hong

Affiliations

  1. 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.
  2. 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. Electronic address: [email protected].

PMID: 33440226 DOI: 10.1016/j.peptides.2021.170494

Abstract

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.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Cholestatic liver disease; Fibrosis; Immune suppression; Regulatory T cell; Substance-P

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