Recombinant human hepassocin stimulates proliferation of hepatocytes in vivo and improves survival in rats with fulminant hepatic failure

Li, Chang‐Yan; Cao, Chuan-Zeng; Xu, Wenjian; Cao, Mengli; Yang, Fan; Dong, Lei; Yu, Miao; Yao, Zhan; Gao, Yabing; Li, Wei; Wang, Zhidong; Ge, Chang‐Hui; Wang, Qing-Ming; Peng, Ruiyun; Yang, Xiaoming

doi:10.1136/gut.2008.171124

Cited by 74 publications

(93 citation statements)

References 27 publications

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“…Research has indicated that FGL1 exerts multiple hepatic protective functions by promoting hepatocyte proliferation and decreasing the rate of apoptosis. A previous study indicated that administration of FGL1 to animals following D-Gal treatment significantly reversed liver injury by promoting hepatocyte proliferation and reducing liver apoptosis, while knockdown of endogenous FGL1 expression exacerbated liver injury (22,23). Concurrent with these results, the present study indicated that the level of FGL1 was enhanced 72 h following the induction of liver injury, indicating that FGL1 was activated upon induction of spontaneous liver regeneration.…”

Section: Discussionsupporting

confidence: 72%

“…FGL1 (also termed FREP1 or hepassocin) is a protein secreted by hepatocytes, which is a member of the fibrinogen family (20). Studies have shown that FGL1 is implicated in liver injury as a mitogenic growth factor and may facilitate damaged liver tissue regeneration and downregulate the expression of proapoptotic factors (21)(22)(23). In the present study, it was hypothesized that intravenous transplantation of BMSCs may increase the expression of FGL1 in the injured rat liver and rescue the liver following acute injury.…”

Section: Introductionmentioning

confidence: 90%

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Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

Zou

Cai

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. In recent years, bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to exert extensive therapeutic effects on acute liver injury; however, the underlying mechanisms of these effects have remained to be elucidated. The present study focused on the potential anti-apoptotic and pro-regenerative effects of BMSCs in D-galactosamine (D-Gal) and lipopolysaccharide (LPS)-induced acute liver injury in rats. An experimental rat acute liver injury model was established by intraperitoneal injection of D-Gal (400 mg/kg) and LPS (80 µg/kg). BMSCs and an identical volume of saline were administered via the caudal vein 2 h after the D-Gal and LPS challenge. Subsequently, the serum samples were collected to detect the levels of alanine aminotransferase and aspartate aminotransferase. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay and immunohistochemical staining were performed to determine apoptosis, regeneration and histological changes of liver sections. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the protein and mRNA expression levels of fibrinogen-like-protein 1 (FGL1), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), STAT3 and B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in liver tissue samples. The results indicated that intravenous transplantation of BMSCs significantly decreased the levels of alanine aminotransferase and aspartate aminotransferase, and reduced hepatocellular necrosis and inflammatory cell infiltration. Additionally, a terminal deoxynucleotidyl transferase-mediated nick-end labeling assay and immunohistochemical staining revealed that BMSC treatment reduced hepatocyte apoptosis and enhanced liver regeneration. Furthermore, Bcl-2 expression was increased, whilst the protein expression of Bax was reduced. The expression of FGL1 and p-STAT3 were elevated concurrently with the improvement of liver function. These results demonstrated that BMSCs may provide a promising potential agent for the prevention of acute liver injury via inhibition of hepatocyte apoptosis and acceleration of liver regeneration. The mechanism may be, a least in part, a consequence of the upregulation of FGL1 expression and the induction of STAT3 phosphorylation.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 90%

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

Zou

Cai

Chen

et al. 2015

Molecular Medicine Reports

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“…To determine whether HPS affected proliferation of hepatoma cells, four hepatoma cell lines were treated with rhHPS, and the growth of these cells were not affected (data not shown), which agreed with the previous studies [Hara and Yoshimura, 2001;Li et al, 2010], suggesting a different mechanism of HPS in the regulation HCC cell growth. To confirm this hypothesis, we transfected HPS expression vector (pcDNA-HPS) or HPS mutant (pcDNA-DN22) into HepG2 cells, and the growth of G418-resistant clones were measured.…”

Section: Hps Inhibits Proliferation Of Hcc Cells Through An Intracrinsupporting

confidence: 83%

“…After 70% hepatectomy of mouse liver, HPS was induced at 2 h and the second peak arrived at 24 h. The expression of HPS maintained high until 72 h and declined to the basal level thereafter. These results indicated that HPS might function as a regulator of hepatocyte growth and be involved in liver regeneration [Li et al, 2010]. On the other hand, studies also have revealed that HPS was associated with progression of liver tumors.…”

mentioning

confidence: 89%

“…These cells were maintained in Dulbecco's modified Eagle's medium (DMEM) or RPMI Medium 1640 (Gibco, Carlsbad, CA) supplemented with penicillin (100 U/ml), streptomycin (10 mg/ml), and 10% fetal bovine serum (MD, St. Louis, MO) at 378C in a humidified incubator with 5% CO 2 in air and split 1:2 at confluence. Recombinant human HPS (rhHPS) was produced as described previously [Li et al, 2010]. G418 was purchased from Calbiochem (San Diego, CA).…”

Section: Cells Cultures and Reagentsmentioning

confidence: 99%

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Hepassocin regulates cell proliferation of the human hepatic cells L02 and hepatocarcinoma cells through different mechanisms

Cao

et al. 2011

J. Cell. Biochem.

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Hepassocin (HPS) is a specific mitogenic active factor for hepatocytes, and inhibits growth by overexpression in hepatocellular carcinoma (HCC) cells. However, the mechanism of HPS regulation on growth of liver-derived cells still remains largely unknown. In this study, we found that HPS was expressed and secreted into the extracellular medium in cultured L02 human hepatic cells; conditional medium of L02 cells promoted proliferation of L02 cells and this activity could be blocked by anti-HPS antibody. Moreover, we identified the presence of receptor for HPS on L02 cells and HepG2 human hepatoma cells. Overproduction of truncated HPS, which signal peptide was deleted, significantly inhibited the proliferation of HCC cells and induced cell cycle arrest. These findings suggest that HPS promotes hepatic cell line L02 cells proliferation via an autocrine mechanism and inhibits HCC cells proliferation by an intracrine pathway.

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Fibrinogen‐like 1: A hepatokine linking liver physiology to hematology

Personnaz,

Guillou,

Kautz

2024

HemaSphere

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A recent study identified the critical contribution of the hepatokine FGL1 to the regulation of iron metabolism during the recovery from anemia. FGL1 is secreted by hepatocytes in response to hypoxia to sequester BMP ligands and repress the transcription of the iron‐regulatory hormone hepcidin. This process ensures the proper supply of iron to the bone marrow for new red blood cell synthesis and the restoration of physiological oxygen levels. FGL1 may therefore contribute to the recovery from common anemias and cause iron overload in chronic anemias with ineffective erythropoiesis, such as ß‐thalassemia, dyserythropoietic anemia, and myelodysplastic syndromes. However, FGL1 has also been described as a regulator of hepatocyte proliferation, glucose homeostasis, and insulin signaling, as well as a mediator of liver steatosis and immune evasion. Chronic exposure to elevated levels of FGL1 during anemia may therefore have systemic metabolic effects besides iron regulation and erythropoiesis. Here, we are providing an overview of the proposed functions of FGL1 in physiology and pathophysiology.

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Recombinant human hepassocin stimulates proliferation of hepatocytes in vivo and improves survival in rats with fulminant hepatic failure

Abstract: HPS is a hepatic growth factor which can accelerate hepatocyte proliferation in vivo and protect against liver injury. These data point to the potential interest of HPS in the treatment of fulminant hepatic failure.

Cited by 74 publications

References 27 publications

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

Hepassocin regulates cell proliferation of the human hepatic cells L02 and hepatocarcinoma cells through different mechanisms

Fibrinogen‐like 1: A hepatokine linking liver physiology to hematology

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