The role of let-7b in the inhibition of hepatic stellate cell activation by rSjP40

PLoS Negl Trop Dis. 2021 Jun 23;15(6):e0009472. doi: 10.1371/journal.pntd.0009472. eCollection 2021 Jun.

Abstract

Background: Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. In this study, we investigated the role of let-7b in the inhibition of HSC activation by rSjP40.

Methods: Expression of let-7b was detected by quantitative real-time PCR. A dual luciferase assay was used to confirm direct interaction between let-7b and collagen I. We also used western blot to assess protein levels of TGFβRI and collagen type I α1 (COL1A1).

Results: We found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b inhibits collagen I expression by directly targeting the 3'UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40.

Conclusion: Our research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antigens, Helminth / genetics
  • Antigens, Helminth / metabolism*
  • Cell Line
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Gene Expression Regulation
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / parasitology
  • Host-Parasite Interactions
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / parasitology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Schistosoma japonicum / genetics
  • Schistosoma japonicum / metabolism*
  • Schistosomiasis japonica / genetics
  • Schistosomiasis japonica / metabolism*
  • Schistosomiasis japonica / parasitology

Substances

  • 3' Untranslated Regions
  • Antigens, Helminth
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Helminth Proteins
  • MicroRNAs
  • Recombinant Proteins
  • mirnlet7 microRNA, human
  • p40 egg antigen, Schistosoma

Grants and funding

This is a project funded by the Research Project of the Health Commission of Jiangsu Province (ZDB2020003, AHL) and the Natural Science Foundation of Nantong City (JC2019036 AHL, JC2020030 XLS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.