Cloning and characterization of a mouse liver-specific gene mfrep-1, upregulated in liver regeneration

Yan, Jun; Ying, Hao; Gu, Fei; He, Jia; Li, Yuli; Liu, Hui Min; Xu, Yong

doi:10.1038/sj.cr.7290137

Cited by 28 publications

(32 citation statements)

References 25 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: 73%

“…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: 89%

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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: 73%

Section: Introductionmentioning

confidence: 89%

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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“…HPS was induced 2 h after a 70% hepatectomy of mouse livers, and the second peak arrived 24 h later. The expression of HPS remained high until 72 h later and declined to the basal level thereafter (3), suggesting that HPS may function as a regulator of cell growth in liver regeneration. Functionally, HPS was initially described as generating mitogenic activity on isolated hepatocytes, whereas it did not promote DNA synthesis in non-liver cell lines in vitro.…”

mentioning

confidence: 94%

“…The position within the human genome is mapped to chromosome 8p22-21. 3. It has been reported that the expression of HPS mRNA was detected mainly in murine livers.…”

mentioning

confidence: 99%

“…Hepassocin (HPS), 3 also called HFREP-1 (hepatocyte-derived fibrinogen-related protein) and fibrinogen-like 1, is a liver-specific gene and belongs to the fibrinogen superfamily, the members of which share a common fibrinogen-like domain at their carboxyl termini (1). HPS is translated into a mature 312-amino acid protein after cleavage of a hydrophobic secretion signal.…”

mentioning

confidence: 99%

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Specific Expression and Regulation of Hepassocin in the Liver and Down-regulation of the Correlation of HNF1α with Decreased Levels of Hepassocin in Human Hepatocellular Carcinoma

et al. 2009

Journal of Biological Chemistry

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Hepassocin (HPS), is a liver-specific gene with mitogenic activity on isolated hepatocytes. It is up-regulated following partial hepatectomy and down-regulated frequently in heptocellular carcinoma (HCC). However, very little is known about the HPS transcription regulation mechanism. In this study, we identified HNF1␣ (hepatocyte nuclear factor-1␣) as an important liver-specific cis-acting element for HPS using in vivo luciferase assays. Deletion of the HNF1 binding site not only led to a complete loss of HPS promoter activity in vivo but also abolished the induction of the HPS promoter by HNF1␣. An electrophoretic mobility shift assay demonstrated that HNF1␣ interacted with the HPS gene promoter in vitro. Chromatin immunoprecipitation showed that HNF1␣ interacted with HMGB1 and CREBbinding protein, and all of them were recruited to the HPS promoter in vivo. Moreover, HNF1␣ expression was lower in HCC cell lines and tissues and correlated significantly with the downregulation of HPS expression. Re-expression of HNF1␣ in human hepatoma HepG2 cells reinduced HPS expression. In contrast, knockdown of endogenous HNF1␣ expression by small interfering RNA resulted in a significant reduction of HPS expression. Furthermore, we found that partial hepatectomy and IL-6 significantly induced promoter activity of HPS, depending on STAT3 and HNF1 binding sites in the HPS promoter. These results demonstrate that the HNF1 binding site and HNF1␣ are critical to liver-specific expression of HPS, and down-regulation or loss of HNF1␣ causes, at least in part, the transcriptional down-regulation of HPS in HCC.

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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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Cloning and characterization of a mouse liver-specific gene mfrep-1, upregulated in liver regeneration

Cited by 28 publications

References 25 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

Specific Expression and Regulation of Hepassocin in the Liver and Down-regulation of the Correlation of HNF1α with Decreased Levels of Hepassocin in Human Hepatocellular Carcinoma

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

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