Wei An

Wei An
Capital Medical University | CCMU · Department of Cell Biology

About

83
Publications
2,244
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1,156
Citations
Citations since 2016
26 Research Items
665 Citations
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
2016201720182019202020212022020406080100120
Introduction
Skills and Expertise

Publications

Publications (83)
Article
Full-text available
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Accumulating evidence indicates that non-alcoholic steatohepatitis (NASH) is a key predisposing factor for HCC occurrence. However, the precise mechanisms driving NASH transition to HCC remain largely obscure. Augmenter of liver regeneration (ALR) is a sulfhydryl oxidas...
Article
Full-text available
Non-alcoholic fatty liver disease (NAFLD) occurs in 25% of the global population and manifests as lipid deposition, hepatocyte injury, activation of Kupffer and stellate cells, and steatohepatitis. Predominantly expressed in hepatocytes, the augmenter of liver regeneration (ALR) is a key factor in liver regulation that can alleviate fatty liver dis...
Preprint
Full-text available
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Accumulating evidence indicates that non-alcoholic steatohepatitis (NASH) is a key predisposing factor for HCC occurrence. However, the precise mechanisms driving NASH transition to HCC remain largely obscure. Augmenter of liver regeneration (ALR) is a sulfhydryl oxidas...
Article
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, characterized by excessive hepatic lipid accumulation. Recently, we demonstrated that Smad ubiquitination regulatory factor 1 (Smurf1) deficiency significantly alleviates mouse hepatic steatosis. However, the mechanism of Smurf1-regulating hepatic lipid accumulat...
Article
The occurrence of liver diseases is attributed to mitochondrial damage. Mitophagy selectively removes dysfunctional mitochondria, thereby preserving mitochondrial function. Augmenter of liver regeneration (ALR) protects the mitochondria from injury. However, whether ALR protection is associated with mitophagy remains unclear. In this study, mitocho...
Article
Cell-based therapeutic approaches have been proven to be effective strategies for the treatment of acute liver injury (ALI). However, widespread application of these procedures is limited by several key issues, including rapid loss of stemness in vitro, aberrant differentiation into undesirable cell types, and low engraftment in vivo. In this study...
Article
Augmenter of liver regeneration (ALR) is an anti‐apoptotic protein found mainly in mitochondria. It protects hepatocytes from ischemia‐reperfusion (I/R) injury, but the underlying mechanism is not clear. We found that in rats, delivery of the ALR gene alleviated hepatic I/R injury during orthotopic liver transplantation as evidenced by reduced seru...
Article
Nonalcoholic fatty liver disease (NAFLD), which is characterized by aberrant accumulation of intrahepatic triglycerides and lipid droplets (LDs) in the liver cells, is becoming increasingly prevalent at an alarming rate worldwide. LDs can be consumed by either hydrolysis or autophagy, which is shown to be of importance in the regulation of hepatic...
Article
Hepatic ischemic reperfusion injury (IRI) is a common complication of liver surgery. Although an imbalance between mitochondrial fission and fusion has been identified as the cause of IRI, the detailed mechanism remains unclear. Augmenter of liver regeneration (ALR) was reported to prevent mitochondrial fission by inhibiting dynamin-related protein...
Article
Full-text available
It is well known that excessive cholesterol accumulation within hepatocytes deteriorates nonalcoholic fatty liver disease (NAFLD). Augmenter of liver regeneration (ALR) has been reported to alleviate NAFLD through anti‐apoptosis; however, whether ALR could protect liver from cholesterol‐induced NAFLD remains unclear. Mice with heterozygous deletion...
Article
Non‐alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders which are characterized by the accumulation of excessive lipid in hepatocytes. The precise pathogenesis of NAFLD is very complicated and remains largely unknown. Smad ubiquitination regulatory factor 1 (Smurf1) is crucial for numerous processes including bone homeos...
Article
Full-text available
Mildly elevated serum bilirubin levels were reported to be associated with decreased risk of non-alcoholic fatty liver disease (NAFLD). Whether this is a causal relationship remains unclear. We tested the hypothesis that genetically elevated plasma bilirubin levels are causally related to reduce risk of NAFLD. A total of 403 eligible participants w...
Article
Alcoholic liver disease is associated with high morbidity and mortality, and treatment options are limited to date. Augmenter of liver regeneration (ALR) may protect against hepatic injury from chemical poisons, including ethanol. Autophagy appears to positively influence survival in cases of liver dysfunction, although the mechanisms are poorly un...
Article
Background: Augmenter of liver regeneration (ALR) protects liver from various injuries, however, the association of ALR with liver fibrosis, particularly its effect on hepatic stellate cells (HSC), remains unclear. In this study, we investigated the impact of ALR on the activation of HSC, a pivotal event in occurrence of liver fibrosis. Methods:...
Article
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to its high frequency of metastasis via the epithelial–mesenchymal transition (EMT) pathway. Hepatic stimulator substance (HSS) can protect hepatocytes from injury and promote liver growth. Recent studies indicated that HSS expression is increased in HCC tissues; however, whe...
Article
The aberrant release of Ca²⁺ from the endoplasmic reticulum (ER) contributes to the onset of ER stress, which is closely related to the pathogenesis of non-alcoholic fatty liver disease. We previously reported that augmenter of liver regeneration (ALR) alleviates ER stress and protects hepatocytes from lipotoxicity. However, the link between ALR pr...
Article
Hepatocellular carcinoma (HCC) is highly chemoresistant and therefore challenges both physicians and patients. Augmenter of liver regeneration (ALR), previously also known as 'hepatic stimulator substance', is reported to inhibit the epithelial-mesenchymal transition (EMT) in HCC, one of the frequent events that occur in cancer metastasis, suggesti...
Article
Full-text available
Background: Fatty liver is 1 of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. Methods: In vivo, liver steatosis of mice...
Article
Ischemia/reperfusion injury, induced by abnormal mitochondrial fission-related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an antiapoptotic effector and could protect liver from ischemia/reperfusion injury. However, the underlying mechanism remain...
Article
Casein kinase 2 interacting protein-1(CKIP-1) is widely expressed in a variety of tissues and cells, and plays an important role in various critical cellular and physiological processes including cell growth, apoptosis, differentiation, cytoskeleton and bone formation. Here, we found: (1) CKIP-1 deficient mice exhibited increased body weight, liver...
Article
Nonalcoholic steatohepatitis (NASH) is characterized by excess accumulation of lipids in liver, accompanied with hepatocyte injury, cell death and inflammation. Although p16is known as tumor suppressor in multiple cancer types, it remains unclear whether p16 plays a critical role in NASH. To determine whether p16 could play a role in the pathogenes...
Article
Nonalcoholic fatty liver disease is considered a disorder of the endoplasmic reticulum (ER) and mitochondria. Recent studies have shown that the ER and mitochondrial membranes overlap by 15–20%, a region referred to as the ‘mitochondria-associated ER membrane’ (MAM). Some proteins, including sarco/ER calcium ATPase (SERCA), are located in the MAM a...
Article
Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease and so-far supposed to be related with mitochondrial impairment. Hepatic stimulator substances (HSS) has been defined as a liver protective factor promoting hepatocyte DNA synthesis and hepatic proliferation after liver intoxication. We previously repo...
Article
Full-text available
Hepatic stimulator substance (HSS), also known as augmenter of liver regeneration (ALR), is a novel hepatic mitogen that stimulates liver regeneration after partial hepatectomy (PH). Recent work has indicated that a lack of ALR expression inhibited liver regeneration in rats; and the mechanism seems to be related with increased cell apoptosis. The...
Article
Full-text available
Recent studies have shown that some glycosyltransferases are involved in the development of nonalcoholic fatty liver disease (NAFLD). The objective of this study was to explore the effect and mechanism of glycosyltransferase GLT8D2 on fatty liver. Rat model of NAFLD was established by induction with high-fat-diet. The GLT8D2 expression in rat liver...
Article
The role of cholesterol in the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unclear. It is known that apoptosis of hepatocytes is an important characteristics of NASH. The objective of this study was to investigate the effects of cholesterol on steatotic HepG2 cell apoptosis and the possible mechanism in vitro. In this study, HepG2...
Article
In the present study, the effective components of anticancer bioactive peptide-3 (ACBP-3), a novel antitumor agent isolated from goat liver, were analyzed. The CD44 (+) fraction of the human gastric cancer cell line was isolated, and the cells within this fraction that could form spheroid colonies (SCs) were identified as gastric cancer stem cells...
Article
HSS (hepatic stimulator substance), also known as ALR (augmenter of liver regeneration), acts as a hepatotrophic growth factor to promote liver regeneration after liver damage or partial hepatectomy. However, the expression and function of HSS during liver development in mammals remain largely unknown. In this work, the hepatoblasts were isolated f...
Article
Full-text available
The aim of this study was to determine the effect and mechanism of tamoxifen (TAM)-induced steatosis in vitro. HepG 2 (Human hepatocellular liver carcinoma cell line) cells were treated with different concentrations of TAM for 72 h. Steatosis of hepatocytes was determined after Oil Red O staining and measurement of triglyceride (TG) concentration....
Article
Hepatic stimulatory substance (HSS), which encodes a sulfhydryl oxidase enzyme, promotes liver regeneration (LR) and maintains the viability of hepatocytes. Surprisingly, we found that the levels of the HSS mRNA and expressed protein were both strongly repressed at 12h after a 70% partial hepatectomy (PH) in mice. Understanding the mechanism and ef...
Article
Although the potential pathogenesis of non-alcoholic fatty liver disease (NAFLD) is unclear, increasing evidence indicates that endoplasmic reticulum (ER) stress may link free fatty acids to NAFLD. Since we previously reported that hepatic stimulator substance (HSS) could protect liver from steatosis. This study is aimed to investigate whether HSS...
Article
Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia/reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of the HSS could attenuate hepatic ischemia/reperfusion injury and the possible mechanisms. Both in vivo...
Article
Full-text available
Fluctuations in serum autofluorescence (AF) intensity have recently been widely used as markers of certain diseases such as cancer. To determine the diagnostic value of serum AF intensity for liver fibrosis in rats, we induced liver fibrosis by subcutaneous injection of carbon tetrachloride into rats. The rat serum AF intensities were detected at t...
Article
The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Hepatocellular apoptosis could be one of the key factors in the pathogenesis of non-alcoholic steatohepatitis (NASH). Hepatic stimulator substance (HSS) protects liver cells from various toxins. We previously reported that HSS is critically impo...
Article
Acute liver failure is a devastating illness of various causes with considerable mortality. Hepatic stimulator substance (HSS) has been suggested for use as a protective agent against acute hepatic injury induced by chemical poisons because it has a variety of biological activities. However, the mechanism whereby HSS protects against hepatotoxins i...
Article
Objective: To select hepatic progenitor cell clones from human fetal liver cells (FLCs) based on α-fetoprotein ( AFP ) promoter activities. Methods: AFP promoter was amplified from human fetal liver genome by polymerase chain reaction (PCR) and cloned into pGL3-basic vector, forming the pGL3-AFP in a direct orientation for the promoters to drive fi...
Article
hHSS (human hepatic stimulator substance), acting as a hepatotrophic growth factor, promotes liver regeneration. However, the regulatory mechanisms for hHSS transcription are still poorly understood. In the present study, we investigated transcription of hHSS triggered by EGF (epidermal growth factor) and the role of C/EBPβ (CCAAT/enhancer-binding...
Article
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD can also p...
Article
Hepatic stimulator substance (HSS) protects liver cells from various toxins by alleviating lesions caused in the mitochondria. This paper demonstrates the necessity of the conserved CXXC catalytic motif (C62–C65) for the mitochondria-targeted anti-apoptotic activity of HSS. Mutating the conserved CXXC motif eliminated the protective effects against...
Article
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to HDL apolipoproteins. We previously reported that unsaturated fatty acids destabilise ABCA1 in murine macrophages and ABCA1-transfected...
Article
Hepatic stimulator substance (HSS) has been shown to protect liver cells from various toxins. However, the mechanism by which HSS protects hepatocytes remains unclear. In this study, we established BEL-7402 cells that stably express HSS and analyzed the protective ability of HSS on cells through mitochondrial permeability (MP). After administration...
Article
Hepatic oval cells, progenitor cells in the liver, can differentiate into hepatocytes and bile duct cells both in vitro and in vivo. Although hepatic stellate cells are another important cell component in the liver, less attention has been focused on the relationship between hepatic oval cells and hepatic stellate cells. Hepatic oval cells were iso...
Article
Uncoupling protein-2 (UCP2) is a mitochondrial inner-membrane carrier protein that is involved in the control of fatty acid metabolism. To understand the mechanism of the transcriptional regulation of ucp2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), we cloned 500 bp upstream of the ucp2 exon 1 from a rat liver cDNA library and ident...
Article
hHSS (human hepatic stimulator substance) stimulates hepatocyte growth. To understand the mechanism controlling hHSS expression, we analysed the proximal promoter activity and identified two regulatory regions (-212/-192 and -152/-132) that were important for transcription in HepG2 cells. Using the luciferase reporter assay, gel-shift experiments a...
Article
Full-text available
Hepatoblasts, which are considered one type of hepatic progenitor cell, reside in the fetal liver. To selectively identify these cells, we transfected primary cultured human fetal liver cells (FLCs) with a pGL3 vector bearing the gene for the enhanced green fluorescence protein (EGFP) under the control of the alpha-fetoprotein (AFP) promoter expres...
Article
Hepatic stimulator substance (HSS) is a novel liver-specific growth-promoting factor. Although HSS has been successfully crystallized, several properties of this protein have yet to be determined. This study shows that recombinant human HSS (rhHSS) is a dimer with a molecular mass of 31 kDa, the protein is weakly acidic and has an isoelectric point...
Article
Hepatic stimulator substance (HSS) protects liver cells from various toxins. However, the mechanism by which HSS protects hepatocytes remains unclear. In this study, we report that the HSS gene, after transfection into BEL-7402 hepatocma cells, is stably expressed in the mitochondria. Hydrogen peroxide (H(2)O(2))-induced cell apoptosis in the HSS-t...
Article
Human hepatic stimulator substance (hHSS) is a newly identified growth-promoting factor in the liver. HSS is capable of stimulating hepatic regeneration in partial hepatectomized rats, thus, promoting growth of hepatic tumor cells. To understand and elucidate the transcriptional regulation of hHSS gene, the 4890bp of 5'-flanking region of the gene...
Article
Liver undergoes profound regeneration usually after hepatic damage. It has been shown in recent study that two kinds of liver stem cells, which are mainly oval cells (OVCs) and small hepatocytes, are involved in the process of liver regeneration as they differentiated into premature liver cells. However, the origination of oval cells as well as its...
Article
To elucidate the effects of sodium butyrate on rat hepatic oval cell differentiation in vitro. Hepatic oval cells were isolated from rats fed with a choline-deficient diet supplemented with 0.1% (w/w) ethonine for 4 to 6 weeks. The cultured hepatic oval cells were identified by immunohistochemistry and reverse transcription-polymerase chain reactio...
Article
To assess the contribution of signal transducer and activator of transcription 3 (JAK-STAT3) pathway, extracellular signal-regulated kinases1/2 (ERK1/2) pathway, and phosphatidylinositol 3-kinase (PI3-K) pathway to cardiomyocytes hypertrophy induced by cardiotrophin-1 (CT-1), a new member of interleukin-6 (IL-6) family of cytokines. STAT3, ERK1/2,...
Article
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway are the two major independent signal transduction pathways. However, it has recently been found that STAT3 may be negatively regulated by ERK1/2 in gp130-dependent signaling. Cardiotrophin-1 (CT-1)...
Article
Signal transducer and activator of transcription 3 (STAT3) is a recently characterized transcription factor which is essential to liver regeneration. We have previously reported that hepatic stimulator substance (HSS), a novel growth-promoting substance, phosphorylated the epidermal growth factor (EGF) receptors and activated downstream Ras-MAP kin...
Article
To investigate protective effects of hHSS transfection against CCl4 or H2O2. cDNA coding for hHSS was constructed into eukaryotic vector of pcDNA3.1 and transfected into BEL-7402 hepatoma cells. The expression of hHSS was analyzed with Northern blot. The growth of the hepatoma cells was remarkably enhanced 24 to 144h after hHSS gene transfection, w...
Article
Human hepatic stimulator substance (hHSS) is a newly identified growth-promoting factor in liver. HSS is capable of stimulating the hepatic regeneration in hepaectomized rats and promoting the growth of hepatic tumor cells. To understand and elucidate the regulation of hHSS on hepatocyte growth at genetic level, the 4,890 bp of 5'-flanking region o...
Article
To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound exp...
Article
The heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme metabolism, has been recently defined as a novel stress-stimulated protein, since the intracellular expression of HO-1 in response to various stimuli as oxidation, ischemia and endotoxin injury has been proved to be able to protect the cells from damage. In this study, a retroviral vector...
Article
To explore the possibility of prokaryotic expression of human hepatic stimulator substance (hHSS), hHSS gene was inserted in the downstream of glutathion S-transferase (GST) in a pET-42a expression vector and recombinant GST-hHSS fusion protein was expressed under IPTG induction in BL-21(DE3) cells. The recombinant HSS was purified with His.Tag aff...
Article
A hepatotropic factor originally identified in weanling or regenerating rat livers, known as hepatic stimulator substance (HSS), is characterized by promoting markedly liver regeneration after partial hepatectomy. Although HSS gene and the gene product have been described recently, the cellular mechanism of HSS and its genetic function remain obscu...
Chapter
Recombinant hepatic stimulator substance (rHSS) was expressed in E. coli by using a bacterial expression vector, which fused a 6 histidin-tag at the N-terminus of rHSS. Protein isolation and purification was performed by Ni2+chromatography. rHSS was found as a homodimer under non-reducing conditions. Additionally endogenous HSS was enriched from we...
Article
To obtain more insight into information of signal transduction of EGF-receptor-mediated pathway response to the stimulation of hepatic stimulator substance (HSS). HSS was extracted from weanling rat liver and partially purified. Bioactivity of HSS was confirmed with its ability to proliferate hepatoma cell in vitro. Meanwhile, a rat recombinant HSS...
Article
The hepatic stimulator substance (HSS) was partially purified from schedule-lighted weanling rat livers. The effects of HSS on p21(ras) expression of human hepatic carcinoma cell BEL-7402 were examined. The results showed: (1) HSS was capable of promoting the proliferation of the cells, and its molecular weight was 14 20 kD; (2) the p21(ras) expres...
Article
The therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system on hepatocellular carcinoma was studied in this experiment. The tk-containing retroviral recombinants were used to infect hepatoma cells (BEL-7402) and the cells were treated with ganciclovir (0-1000 microg/ml). The results showed that HSV-tk gene could...