Syndecan‐1 limits the progression of liver injury and promotes liver repair in acetaminophen‐induced liver injury in mice

Nam, Eon Jeong; Hayashida, Kazutaka; Aquino, Rafael Santos de; Couchman, John R.; Kozar, Rosemary A.; Liu, Jian; Park, Pyong Woo

doi:10.1002/hep.29265

Cited by 34 publications

(33 citation statements)

References 54 publications

(131 reference statements)

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“…In the decision making process MELD score is a helpful tool to establish the severity of the disease and predicts 3month mortality among patients with chronic liver disease waiting for transplantation [19]. In in vivo experiment syndecan-1 attenuated acetaminophen induced acute liver failure and promoted liver repair in mice [20]. In our study enhanced MELD score groups went together with higher amount of syndecan-1 on hepatocyte surface.…”

Section: Discussionsupporting

confidence: 49%

Syndecan-1 in Liver Diseases

Regős

Karászi

Reszegi

et al. 2019

Pathol. Oncol. Res.

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Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans in the liver. Syndecan-1 is normally expressed on the surfaces of hepatocytes and cholangiocytes. Due to liver diseases the amount of syndecan-1 increases in the liver. Despite the emerging data of the biological function of syndecan-1, the clinical usefulness of this proteoglycan is still unknown. In our study we correlated syndecan-1 expression to clinico-pathological data. We found that syndecan-1 proved to be a good marker for hepatitis C virus based hepatocellular carcinoma and increased with liver dysfunction.

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Section: Discussionsupporting

confidence: 49%

Syndecan-1 in Liver Diseases

Regős

Karászi

Reszegi

et al. 2019

Pathol. Oncol. Res.

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“…The Akt/mTOR pathway is an important signaling pathway in regulating the intracellular homeostasis. It is reported that the activation of Akt signal pathway further can facilitate liver repair and regeneration [ 47 ] and attenuates APAP-induced liver injury [ 48 ]. A recent study has shown that activation of Akt/mTOR signaling pathway is essential in the inhibition of autophagy [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis

Yan

Sun

Ren

et al. 2018

IJMS

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Acetaminophen overdose-induced hepatotoxicity is the most common cause of acute liver failure in many countries. Previously, alpha-mangostin (α-MG) has been confirmed to exert protective effects on a variety of liver injuries, but the protective effect on acetaminophen-induced acute liver injury (ALI) remains largely unknown. This work investigated the regulatory effect and underlying cellular mechanisms of α-MG action to attenuate acetaminophen-induced hepatotoxicity in mice. The increased serum aminotransferase levels and glutathione (GSH) content and reduced malondialdehyde (MDA) demonstrated the protective effect of α-MG against acetaminophen-induced hepatotoxicity. In addition, α-MG pretreatment inhibited increases in tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) caused by exposure of mice to acetaminophen. In liver tissues, α-MG inhibited the protein expression of autophagy-related microtubule-associated protein light chain 3 (LC3) and BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3). Western blotting analysis of liver tissues also proved evidence that α-MG partially inhibited the activation of apoptotic signaling pathways via increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase 3 proteins. In addition, α-MG could in part downregulate the increase in p62 level and upregulate the decrease in p-mTOR, p-AKT and LC3 II /LC3 I ratio in autophagy signaling pathways in the mouse liver. Taken together, our findings proved novel perspectives that detoxification effect of α-MG on acetaminophen-induced ALI might be due to the alterations in Akt/mTOR pathway in the liver.

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“…The lack of relevance of apoptosis in APAP‐induced hepatotoxicity is further supported by the evidence that the pan‐caspase inhibitor did not improve APAP‐induced liver injury . It should be noted that a small amount of apoptosis was observed in certain genetic knockout (KO) mouse strains such as syndecan‐1, liver specific Atg7 or Atg5 knockout mice . The apoptosis observed in these KO mice could be due to the secondary effects as a result of the deletion of the gene in the liver such as the activation of Nrf2 in liver‐specific Atg5 KO mice .…”

Section: Apap Metabolism and Hepatotoxicitymentioning

confidence: 97%

“…17 It should be noted that a small amount of apoptosis was observed in certain genetic knockout (KO) mouse strains such as syndecan-1, liver specific Atg7 or Atg5 knockout mice. [18][19][20] The apoptosis observed in these KO mice could be due to the secondary effects as a result of the deletion of the gene in the liver such as the activation of Nrf2 in liver-specific Atg5 KO mice. 19 Therefore, it should be cautious to interpret data obtained from gene KO mice in APAP-induced liver injury.…”

Section: C-jun N-terminal Kinasementioning

confidence: 99%

Role and mechanisms of autophagy in acetaminophen‐induced liver injury

Chao

Wang

Jaeschke

et al. 2018

Liver International

124

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Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the USA and many other countries. Although the metabolism and pathogenesis of APAP has been extensively investigated for decades, the mechanisms by which APAP induces liver injury are incompletely known, which hampers the development of effective therapeutic approaches to tackle this important clinical problem. Autophagy is a highly conserved intracellular degradation pathway, which aims at recycling cellular components and damaged organelles in response to adverse environmental conditions and stresses as a survival mechanism. There is accumulating evidence indicating that autophagy is activated in response to APAP overdose in specific liver zone areas, and pharmacological activation of autophagy protects against APAP-induced liver injury. Increasing evidence also suggests that hepatic autophagy is impaired in nonalcoholic fatty livers (NAFLD), and NAFLD patients are more susceptible to APAP-induced liver injury. Here, we summarized the current progress on the role and mechanisms of autophagy in protecting against APAP-induced liver injury.

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Syndecan‐1 limits the progression of liver injury and promotes liver repair in acetaminophen‐induced liver injury in mice

Cited by 34 publications

References 54 publications

Syndecan-1 in Liver Diseases

Syndecan-1 in Liver Diseases

Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis

Role and mechanisms of autophagy in acetaminophen‐induced liver injury

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