Review
Pathophysiological role of prostaglandin E synthases in liver diseases

https://doi.org/10.1016/j.prostaglandins.2021.106552Get rights and content

Highlights

  • PGESs, especially mPGES-1 and mPGES-2, play important roles in the pathogenesis of liver diseases.

  • mPGES-1, an inflammation-inducible PGES, is involved in different liver diseases.

  • mPGES-2 has opposite effects on the liver disease models induced by STZ and APAP.

  • mPGES-1 may serve as a promising target for treating liver diseases because of less side effects.

Abstract

Prostaglandin E synthases (PGESs) convert cyclooxygenase (COX)-derived prostaglandin H2 (PGH2) into prostaglandin E2 (PGE2) and comprise at least three types of structurally and biologically distinct enzymes. Two of these, namely microsomal prostaglandin E synthase-1 (mPGES-1) and mPGES-2, are membrane-bound enzymes. mPGES-1 is an inflammation-inducible enzyme that converts PGH2 into PGE2. mPGES-2 is a bifunctional enzyme that generally forms a complex with haem in the presence of glutathione. This enzyme can metabolise PGH2 into malondialdehyde and can produce PGE2 after its separation from haem. In this review, we discuss the role of PGESs, particularly mPGES-1 and mPGES-2, in the pathogenesis of liver diseases. A better understanding of the roles of PGESs in liver disease may aid in the development of treatments for patients with liver diseases.

Introduction

PGE synthase (PGES) is a terminal enzyme that synthesises prostaglandin E2 (PGE2). PGE2 is one of the most common prostanoids produced by many cells and tissues and is important in metabolism. In addition to PGESs, upstream phospholipase A2 and cyclooxygenase (COX) play important roles in the synthesis of PGE2 [[1], [2], [3]]. Three types of PGESs, namely microsomal PGES-1 (mPGES-1) and -2 (mPGES-2) and cytosolic PGES, have been discovered to be involved in PGE2 synthesis. However, the role of cytosolic PGES in the development of liver diseases remains unclear. mPGES-1 and mPGES-2 were found to be expressed in the liver and involved in liver disease [4,5]. Notably, mice with related enzyme deletions have been engineered for further research of their pathophysiological roles [6]. This review summarises the roles of the PGESs, particularly mPGES-1 and mPGES-2, in liver diseases such as viral hepatitis and Fas- and lipopolysaccharide (LPS)-induced liver injury.

Section snippets

Prostaglandin e synthases (PGESs)

mPGES-1 is a glutathione (GSH)-dependent membrane-bound enzyme that was initially detected in LPS-stimulated macrophages in 1999 [7]. It is expressed at low levels in normal tissues but at higher levels in inflamed tissues [8]. Among PGESs, only mPGES-1 is highly expressed in the presence of a proinflammatory stimulus [1]. Although COX-2 was once regarded as a useful target for treated related liver diseases, its targeting has been reported to cause many side effects, particularly in the renal

Conclusion

In this review, we summarise the role of PGESs, mPGES-1, and mPGES-2 in different types of liver diseases, such as viral hepatitis, NAFLD, Fas-induced injury, and drug-induced injury. However, the specific function of mPGES-1 in inflammation is unclear because the role of mPGES-1 differs in inflammation caused by different proinflammatory factors [18,24,30]. Currently, related studies indicate that mPGES-1 deficiency contributes to the recovery from liver injury or tumour clearance [47].

Declaration of Competing Interest

The authors declare that they have no conflicts of interest.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 81603179), China Postdoctoral Science Special Foundation (grant no. 2018T110555), and Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (grant no. PPZY2015B161).

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    These authors contributed equally to this work.

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