Dataset Information

Mesenchymal stem cell-secreted prostaglandin E₂ ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization.

ABSTRACT:

Background

Acute liver failure (ALF) is an acute inflammatory liver disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) is a promising therapeutic approach; however, the effect is not satisfied as the underlying molecular mechanisms of MSC in treating ALF remain unclear.

Methods

MSC isolated from 4- to 6-week-old C57BL/6 mice were used to treat ALF. Histological and serological parameters were analyzed to evaluate the efficacy of MSC. We explored the molecular mechanism of MSC in the treatment of ALF by detecting liver inflammatory response and hepatocyte death.

Results

In this study, we found that the therapeutic potential of MSC on ALF is dependent on the secretion of prostaglandin E₂ (PGE₂), a bioactive lipid. MSC-derived PGE₂ inhibited TGF-?-activated kinase 1 (TAK1) signaling and NLRP3 inflammasome activation in liver macrophages to decrease the production of inflammatory cytokines. Meanwhile, macrophages in the liver could be induced to anti-inflammatory (M2) macrophages by MSC-derived PGE₂ via STAT6 and mechanistic target of rapamycin (mTOR) signaling, which then promote inflammatory resolution and limit liver injury. Finally, administrating EP4 antagonist significantly ameliorated the therapeutic ability of MSC, which promoted liver inflammation and decreased M2 macrophages.

Conclusions

Our results indicate that PGE₂ might be a novel important mediator of MSC in treating ALF, which is through inhibiting the liver inflammatory response and hepatocyte death.

SUBMITTER: Wang J

PROVIDER: S-EPMC7792134 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Mesenchymal stem cell-secreted prostaglandin E<sub>2</sub> ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization.

Wang Jinglin J Liu Yang Y Ding Haoran H Shi Xiaolei X Ren Haozhen H

Stem cell research & therapy 20210107 1

<h4>Background</h4>Acute liver failure (ALF) is an acute inflammatory liver disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) is a promising therapeutic approach; however, the effect is not satisfied as the underlying molecular mechanisms of MSC in treating ALF remain unclear.<h4>Methods</h4>MSC isolated from 4- to 6-week-old C57BL/6 mice were used to treat ALF. Histological and serological parameters were analyzed to evaluate t ...[more]

PMID: 33413632

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