Monocyte Chemoattractant Protein‐Induced Protein 1 Targets Hypoxia‐Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury

Sun, Peng; Lu, Yingfeng; Cheng, Daqing; Zhang, Kuo; Zheng, Jilin; Liu, Yupeng; Wang, Xiaozhan; Yua, Yuan; Tang, Yi-Da

doi:10.1002/hep.30086

Cited by 31 publications

(22 citation statements)

References 42 publications

(109 reference statements)

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“…It was also shown that overexpression of Mcpip1 reduces liver injury in septic mice, by inhibiting inflammatory reaction in macrophages [15]. Additionally, Mcpip1 ameliorates liver damage, reduces inflammation, and promotes tissue regeneration in the hepatic ischemia/reperfusion injury model [16].…”

Section: Introductionmentioning

confidence: 97%

Role of Mcpip1 in obesity-induced hepatic steatosis as determined by myeloid and liver-specific conditional knockouts

Pydyn

Żurawek

Kozieł

et al. 2020

Preprint

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Background&AimsMonocyte chemoattractant protein-induced protein 1 (MCPIP1, alias Regnase1) is a negative regulator of inflammation, acting through cleavage of transcripts coding for proinflammatory cytokines and by inhibition of NFκB activity. Moreover, it was demonstrated, that MCPIP1 regulates lipid metabolism both in adipose tissue and hepatocytes. In this study, we investigated the effects of tissue-specific Mcpip1 deletion on the regulation of hepatic metabolism and development of non-alcoholic fatty liver disease (NAFLD).MethodsWe used mice with deletion of Mcpip1 in myeloid leukocytes (Mcpip1LysMKO) and in hepatocytes (Mcpip1AlbKO), which were fed chow or a high-fat diet (HFD) for 12 weeks.ResultsMcpip1LysMKO mice which were fed a chow diet were characterized by a significantly reduced hepatic expression of genes regulating lipid and glucose metabolism, which was followed by hypoglycemia and dyslipidemia. These animals also developed systemic inflammation, manifested by increased concentrations of cytokines in the plasma. On the other hand, there were no significant changes in phenotype in Mcpip1AlbKO mice. Although we detected a reduced hepatic expression of genes regulating glucose metabolism and β-oxidation in these mice, they remained asymptomatic. Upon feeding them a HFD, Mcpip1LysMKO mice did not develop obesity, glucose intolerance, nor hepatic steatosis, but were characterized by hypoglycemia and dyslipidemia, along with proinflammatory phenotype with symptoms of cachexia. Mcpip1AlbKO animals, following a HFD, became hypercholesterolemic, but accumulated lipids in the liver at the same level as Mcpip1fl/fl mice, and had no changes in the level of soluble factors tested in the plasma.ConclusionsIn conclusion, we have demonstrated that Mcpip1 protein plays an important role in the development of fatty liver disease, hepatitis, and during NAFLD progression. Depletion of Mcpip1 in myeloid leukocytes, followed by systemic inflammation, has a more pronounced effect on controlling liver metabolism and homeostasis than the depletion of Mcpip1 in hepatocytes.

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Section: Introductionmentioning

confidence: 97%

Role of Mcpip1 in obesity-induced hepatic steatosis as determined by myeloid and liver-specific conditional knockouts

Pydyn

Żurawek

Kozieł

et al. 2020

Preprint

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“…Hepatic ischemia-reperfusion (I/R) injury is a complication of hepatic surgery, and it can arise after liver resection and transplantation [1,2]. Hepatic I/R injury induces oxidative stress, inflammation, and other disorders in the liver, thus leading to the liver damage in patients requiring liver surgery [3][4][5][6]. However, the mechanisms underlying the I/R injury are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Guo

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Hepatic ischemia-reperfusion (I/R) injury is a serious complication in patients who have undergone hepatic surgery such as orthotopic liver transplantation and partial hepatectomy. Recently, a new cytoprotective agent, ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), was reported to protect against hepatic I/R injury. However, the protective mechanism of UDCA-LPE is not fully understood. Therefore, we conducted this study to explore its underlying mechanism. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the liver lipid metabolism changes in mice during I/R. KEGG enrichment indicated that UDCA-LPE is likely to exert its protective role by regulating fatty acid (FA) metabolism. Further analysis found that UDCA-LPE significantly increased the ratio of oleic acid (OA) to palmitic acid (PA). We found that mice pretreated with OA improved tolerance to hepatic I/R injury. In addition, the phosphorylation level of AKT was markedly upregulated during oxidative stress to promote p65 nuclear translocation, triggering an inflammatory response that exacerbated cell damage and OA treatment significantly inhibited this process. Notably, OA was found to inhibit H2O2-induced oxidative stress, inflammation, and cell death in HepG2 cells. Furthermore, we found that OA supplementation to the medium did not result in a significant increase in intracellular OA, but marked increase in the ratio of OA to PA, which may be an important mechanism for the inflammatory response induced by oxidative stress during I/R. Finally, we demonstrated that OA increased the level of autophagy in HepG2 cells, which may be one of the protective mechanisms against oxidative stress. Collectively, this study revealed that FA metabolism functionally determines the oxidative stress-related inflammation caused by hepatic I/R. We hypothesize that OA treatment may be a promising strategy for preventing and treating I/R-induced liver damage.

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“…Last, in extension to the measured AST and ALT levels, a more comprehensive evaluation of the functional outcomes such as short-and long-term survival after liver injury should be part of future studies. Furthermore, for a deeper understanding of the underlying mechanisms of hepatic regeneration after IRI, evaluation of protein levels such as HIF1-α might be an objective for further studies [27].…”

Section: Discussionmentioning

confidence: 99%

“…Paraffin-embedded liver sections for immunohistochemistry were immersed in three changes of xylene and hydrated with a graded series of alcohol. Hematoxylin and eosin staining (H&E) was used to evaluate the regenerative capacity of the liver by determination of Mitotic Index and the liver damage by Suzuki's score [27]. Suzuki's score was obtained by a single blinded pathologist experienced in liver histology.…”

Section: Histologymentioning

confidence: 99%

Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats

Schmitz

Dohmeier

Stoppe

et al. 2020

IJMS

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Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1β, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1β and IL-6 was significantly higher after argon inhalation after 36 h (IL-1β 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1β and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

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Monocyte Chemoattractant Protein‐Induced Protein 1 Targets Hypoxia‐Inducible Factor 1α to Protect Against Hepatic Ischemia/Reperfusion Injury

Cited by 31 publications

References 42 publications

Role of Mcpip1 in obesity-induced hepatic steatosis as determined by myeloid and liver-specific conditional knockouts

Role of Mcpip1 in obesity-induced hepatic steatosis as determined by myeloid and liver-specific conditional knockouts

Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways

Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats

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