Soluble fibrinogen‐like protein 2 ameliorates acute rejection of liver transplantation in rat via inducing Kupffer cells M2 polarization

Pan, Guangrui; Zhao, Zhenxing; Tang, Chengyong; Ding, Liuyue; Li, Zhongtang; Zheng, Daofeng; Zong, Liang; Wu, Zhongjun

doi:10.1002/cam4.1528

Cited by 22 publications

(17 citation statements)

References 41 publications

(80 reference statements)

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“…Soluble fibrinogen-like protein 2 (sFGL2) promotes the secretion of anti-inflammatory cytokines (IL-10, TGF-β) and the high expression of CD206 and inhibits the activity of STAT1 and NF-κB signaling pathways. sFGL2 improves the prognosis of LT by inducing KC M2 polarization in rat orthotropic liver transplantation (OLT) models (25).…”

Section: Polarization Of Kcs In I/rmentioning

confidence: 99%

Effect of Hepatic Macrophage Polarization and Apoptosis on Liver Ischemia and Reperfusion Injury During Liver Transplantation

Mao

et al. 2020

Front. Immunol.

103

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Ischemia-reperfusion (I/R) injury is injury caused by a limited blood supply and subsequent blood supply recovery during liver transplantation. Serious ischemia-reperfusion injury is the main cause of transplant failure. Hepatic I/R is characterized by tissue hypoxia due to a limited blood supply and reperfusion inducing oxidative stress and an immune response. Studies have confirmed that Kupffer cells (KCs), resident macrophages in the liver, play a key role in aseptic inflammation induced by I/R. In liver macrophage polarization, M1 macrophages activated by interferon-γ (IFN-γ) and lipopolysaccharide (LPS) exert a pro-inflammatory effect and release a variety of inflammatory cytokines. M2 macrophages activated by IL-4 have an anti-inflammatory response. M1-type KCs are the dominant players in I/R as they secrete various pro-inflammatory cytokines that exacerbate the injury and recruit other types of immune cells via the circulation. In contrast, M2-type KCs can ameliorate I/R through unregulated anti-inflammatory factors. A new notion has been proposed that KC apoptosis may influence I/R in yet another manner as well. Management of KCs is expected to help improve I/R. This review summarizes the effects of hepatic macrophage polarization and apoptosis on liver I/R.

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Section: Polarization Of Kcs In I/rmentioning

confidence: 99%

Effect of Hepatic Macrophage Polarization and Apoptosis on Liver Ischemia and Reperfusion Injury During Liver Transplantation

Mao

et al. 2020

Front. Immunol.

103

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“…FGL2 in hepatocellular carcinoma may help maintaining the undifferentiated state of bone marrow cells directly via FcγRIIB, and therefore promote the accumulation of MDSCs required for tumor growth. FGL2 may also upregulate the expression of several cytokines, including tumor growth factor β and interleukin 6 ( 46 , 47 ), in the human hepatocellular carcinoma tumor microenvironment in order to promote the maintenance and recruitment of MDSCs. FGL2 may also induce the accumulation of MDSCs by direct and indirect mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Fibrinogen‑like protein 2 promotes the accumulation of myeloid‑derived suppressor cells in the hepatocellular carcinoma tumor microenvironment

et al. 2020

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The tumor microenvironment in hepatocellular carcinoma can be classified into cellular and non-cellular components. Myeloid-derived suppressor cells (MDSCs) are cellular components of this microenvironment that serve an important role in the progression of hepatocellular carcinoma. Fibrinogen-like protein 2 (FGL2) has been demonstrated to promote tumor progression by regulating cellular components of the tumor microenvironment in various types of malignant tumor. The present study aimed to determine the expression of FGL2 in hepatocellular carcinoma and its effect on the tumor microenvironment in order to determine novel targets for liver cancer treatment. Immunohistochemistry and reverse transcription quantitative PCR were performed to determine the expression level of FGL2 and the correlation with surface markers of human MDSCs in hepatocellular carcinoma. Furthermore, a mouse hepatocellular carcinoma cell line overexpressing FGL2 was established by stable transfection of a lentivirus expressing FGL2. In addition, fresh bone marrow cells extracted from mouse femurs were in vitro cultured using conditioned medium derived from the cell line overexpressing FGL2. An orthotopic hepatocellular carcinoma mouse model was also established. The results demonstrated that FGL2 expression level in hepatocellular carcinoma tissues was closely associated with tumor size. FGL2 level was positively correlated with the expression level of the MDSC surface markers CD11b and CD33 in hepatocellular carcinoma. The in vitro results demonstrated that FGL2 could maintain the undifferentiated state of bone marrow cells, therefore promoting MDSC accumulation. Furthermore, in the orthotopic hepatocellular carcinoma mouse model, we observed that overexpression of FGL2 could promote tumor growth and significantly increase the number of MDSCs in the tumors and spleen. Taken together, these findings suggested that FGL2 may promote hepatocellular carcinoma tumor growth by promoting the accumulation of MDSCs in the tumor microenvironment.

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“…To deplete Kcs in the donor livers, clodronate liposomes (cLs) were used as before (37). Then KCs (2x10 7 cells) that were isolated from the liver tissue of AAV-ATG5-shRNA-or scramble-treated rats, were injected into recipients via the portal vein during OLT (38).…”

Section: Establishment Of the Rat Hiri Model With Atg5 Knockdown Inmentioning

confidence: 99%

Suberoylanilide hydroxamic acid alleviates orthotopic liver transplantation‑induced hepatic ischemia‑reperfusion injury by regulating the AKT/GSK3β/NF‑κB and AKT/mTOR pathways in rat Kupffer cells

Wang

Deng

et al. 2020

Int J Mol Med

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Multiple mechanisms are involved in regulating hepatic ischemia-reperfusion injury (IRI), in which Kupffer cells (Kcs), which are liver-resident macrophages, play critical roles by regulating inflammation and the immune response. Suberoylanilide hydroxamic acid (SAHA), a pan-histone deacetylase inhibitor, has anti-inflammatory effects and induces autophagy. To investigate whether SAHA ameliorates IRI and the mechanisms by which SAHA exerts its effects, an orthotopic liver transplantation (OLT) rat model was established after treatment with SAHA. The results showed that SAHA effectively ameliorated OLT-induced IRI by reducing M1 polarization of Kcs through inhibition of the AKT/glycogen synthase kinase (GSK)3β/NF-κB signaling pathway. Furthermore, the present study found that SAHA upregulates autophagy 5 protein (ATG5)/Lc3B in Kcs through the AKT/mTOR signaling pathway and inhibition of autophagy by knockdown of ATG5 in Kcs partly impaired the protective effect of SAHA on IR-injured liver. Therefore, the current study demonstrated that SAHA reduces M1 polarization of Kcs by inhibiting the AKT/GSK3β/NF-κB pathway and upregulates autophagy in Kcs through the AKT/mTOR signaling pathway, which both alleviate OLT-induced IRI. The present study revealed that SAHA may be a novel treatment for the amelioration of OLT-induced IRI.

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Soluble fibrinogen‐like protein 2 ameliorates acute rejection of liver transplantation in rat via inducing Kupffer cells M2 polarization

Cited by 22 publications

References 41 publications

Effect of Hepatic Macrophage Polarization and Apoptosis on Liver Ischemia and Reperfusion Injury During Liver Transplantation

Effect of Hepatic Macrophage Polarization and Apoptosis on Liver Ischemia and Reperfusion Injury During Liver Transplantation

Fibrinogen‑like protein 2 promotes the accumulation of myeloid‑derived suppressor cells in the hepatocellular carcinoma tumor microenvironment

Suberoylanilide hydroxamic acid alleviates orthotopic liver transplantation‑induced hepatic ischemia‑reperfusion injury by regulating the AKT/GSK3β/NF‑κB and AKT/mTOR pathways in rat Kupffer cells

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