Toll-like receptor 5-mediated signaling enhances liver regeneration in mice

Wen Zhang; Lei Wang; Xue-Hua Sun; Xian Liu; Yang Xiao; Jie Zhang; Ting Wang; Hui Chen; Yi-Qun Zhan; Miao Yu; Chang-Hui Ge; Chang-Yan Li; Guang-Ming Ren; Rong-Hua Yin; Xiao-Ming Yang

doi:10.1186/s40779-021-00309-4

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Toll-like receptor 5-mediated signaling enhances liver regeneration in mice

RESEARCH | Updated：2023-02-28

- Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
- Military Medical Research Vol. 8, Issue 4, Pages: 490-502(2021)
- Affiliations：
  
  1.Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  2.State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
  3.School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
  4.Beijing Institute of Radiation Medicine, Beijing 100850, China
- Author bio：
  
  * max19920503@163.com;
  yrh1980110@126.com;
  xiaomingyang@sina.com
- Funds：
- DOI：10.1186/s40779-021-00309-4
  CLC：
- Published：2021-12
- Accepted：
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Zhang et al.: Toll-like receptor 5-mediated signaling enhances liver regeneration in mice. Mil Med Res, 2021, 8: 16.
DOI：

Zhang et al.: Toll-like receptor 5-mediated signaling enhances liver regeneration in mice. Mil Med Res, 2021, 8: 16. DOI： 10.1186/s40779-021-00309-4.

摘要

Abstract

Background:

Toll-like receptor 5 (TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases. However

the role of TLR5 in experimental models of liver regeneration has not been reported. This study aimed to investigate the role of TLR5 in partial hepatectomy (PHx)-induced liver regeneration.

Methods:

We performed 2/3 PHx in wild-type (WT) mice

TLR5 knockout mice

or TLR5 agonist CBLB502 treated mice

as a model of liver regeneration. Bacterial flagellin content was measured with ELISA

and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry. To study the effects of TLR5 on hepatocyte proliferation

we analyzed bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression with immunohistochemistry (IHC) staining. The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels

and with Western blotting analysis of hepatic NF-κB and STAT3 activation. Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array (CBA) assays. Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.

Results:

The bacterial flagellin content in the serum and liver increased

and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx. TLR5-deficient mice exhibited diminished numbers of BrdU- and PCNA-positive cells

suppressed immediate early gene expression

and decreased cytokine and growth factor production. Moreover

PHx-induced hepatic NF-κB and STAT3 activation was inhibited in

Tlr5

–/–

mice

as compared with WT mice. Consistently

the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation

which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver. Furthermore

Tlr5

–/–

mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.

Conclusions:

We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx. Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.

关键词

Keywords

references

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