The regulatory role of prostaglandin E2in liver (patho) physiology is controlled at its site of synthesis and its action on the receptors

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of "most targeted receptors". About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases

Dwivedi

Datta

El‐Kersh

et al. 2023

The FASEB Journal

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Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury

Chen

Han

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme for the synthesis of prostaglandin E2 (PGE2), a proproliferative and antiapoptotic lipid molecule important for tissue regeneration and injury repair. In this study, we developed transgenic (Tg) mice with targeted expression of mPGES-1 in the liver to assess Fas-induced hepatocyte apoptosis and acute liver injury. Compared with wild-type (WT) mice, the mPGES-1 Tg mice showed less liver hemorrhage, lower serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, less hepatic necrosis/apoptosis, and lower level of caspase cascade activation after intraperitoneal injection of the anti-Fas antibody Jo2. Western blotting analysis revealed increased expression and activation of the serine/threonine kinase Akt and associated antiapoptotic molecules in the liver tissues of Jo2-treated mPGES-1 Tg mice. Pretreatment with the mPGES-1 inhibitor (MF63) or the Akt inhibitor (Akt inhibitor V) restored the susceptibility of the mPGES-1 Tg mice to Fas-induced liver injury. Our findings provide novel evidence that mPGES-1 prevents Fas-induced liver injury through activation of Akt and related signaling and suggest that induction of mPGES-1 or treatment with PGE2 may represent important therapeutic strategy for the prevention and treatment of Fas-associated liver injuries.

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Rebamipide retards CCl₄-induced hepatic fibrosis in rats: Possible role for PGE₂

Zakaria

El‐Sisi

2016

Journal of Immunotoxicology

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Prostaglandin E 2 (PGE 2 ) is a potent physiological suppressor of liver fibrosis. Because the anti-ulcer drug rebamipide can induce the formation of endogenous PGE 2 , this study investigated the potential effects of rebamipide on development of a hepatic fibrosis that was inducible by carbon tetrachloride (CCl 4 ). Groups of Wistar rats received intraperitoneal (IP) injections of CCl 4 (0.45 ml/kg [0.72 g CCl 4 /kg]) over the course of for 4 weeks. Sub-sets of CCl 4 -treated rats were also treated concurrently with rebamipide at 60 or 100 mg/kg. At 24 h after the final treatments, liver function and oxidative stress were indirectly assessed. The extent of hepatic fibrosis was evaluated using two fibrotic markers, hyaluronic acid (HA) and pro-collagen-III (Procol-III); isolated liver tissues underwent histology and were evaluated for interleukin (IL)-10 and PGE 2 content. The results indicated that treatment with rebamipide significantly inhibited CCl 4 -induced increases in serum ALT and AST and also reduced oxidative stress induced by CCl 4 . Fibrotic marker assays revealed that either dose of rebamipide decreased the host levels of Procol-III and HA that had become elevated due to the CCl 4 . At the higher dose tested, rebamipide appeared to be able to permit the hosts to have a normal liver histology and to minimize any CCl 4 -induced collagen precipitation in the liver. Lastly, the use of rebamipide was seen to be associated with significant increases in liver levels of both PGE 2 and the anti-inflammatory cytokine IL-10. Based on these findings, it is concluded that rebamipide can retard hepatic fibrosis induced by CCl 4 and that this effect may, in part, be mediated by an induction of PGE 2 and IL-10 in the liver itself. ARTICLE HISTORY

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The regulatory role of prostaglandin E2in liver (patho) physiology is controlled at its site of synthesis and its action on the receptors

Cited by 4 publications

References 0 publications

GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases

GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases

Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury

Rebamipide retards CCl₄-induced hepatic fibrosis in rats: Possible role for PGE₂

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The regulatory role of prostaglandin E2in liver (patho) physiology is controlled at its site of synthesis and its action on the receptors

Cited by 4 publications

References 0 publications

GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases

GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases

Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury

Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2

Contact Info

Product

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Rebamipide retards CCl₄-induced hepatic fibrosis in rats: Possible role for PGE₂