Hepatocyte nuclear factor 1B mutation in a Chinese family with renal cysts and diabetes syndrome:A case report

BACKGROUND Renal cysts and diabetes(RCAD)syndrome is an autosomal dominant diabetic renal disease.Precise molecular diagnosis of RCAD syndrome has proven valuable for understanding its mechanism and personalized therapy.CASE SUMMARY A RCAD patient and her family were studied to investigate potential responsible genes by the whole exome sequencing(WES).Candidate pathogenic variants were validated by Sanger sequencing.The clinical characteristics of RCAD patient were collected from medical records.Unlike those typical RCAD patients,we observed renal manifestation and prediabetes phenotype,but not reproductive organ phenotype and hypomagnesaemia.A novel 7-bp deletion mutation in exon 4 of the hepatocyte nuclear factor 1B,NM_000458:c.882_888del(p.V294fs),was identified by WES and confirmed by Sanger sequencing.CONCLUSION This novel mutation identified in a Chinese family with RCAD syndrome might be the molecular pathogenic basis of this disorder.

Berberine retarded the growth of gastric cancer xenograft tumors by targeting hepatocyte nuclear factor 4α

BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is increasing every year due to aging and the growth of high-risk populations,and gastric cancer is still a leading cause of cancer-related death.Gastric cancer is a consequence of the complex interaction of microbial agents,with environmental and host factors,resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways.Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers.Trastuzumab,a monoclonal antibody against the HER2 receptor,is approved in the first-line treatment of patients with HER2+tumors,which accounts for 13%-23%of the gastric cancer population.Ramucirumab,a monoclonal antibody against VEGFR2,is currently recommended in patients progressing after first-line treatment.Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with dis-appointing results,such as anti-EGFR and anti-MET monoclonal antibodies.Therefore,it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets.AIM To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α(HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine.METHODS MGC803 and SGC7901 subcutaneous xenograft models were established.The control group was intragastrically administrated with normal saline,and the berberine group was administrated intragastrically with 100 mg/kg/d berberine.The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction.The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors.Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.Western blotting and IHC were performed to assess the protein expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.RESULTS In the both MGC803 and SGC7901 xenograft tumor models,berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors.In the SGC7901 and MGC803 subcutaneously transplanted tumor models,berberine down-regulated the expression of HNF4α,WNT5a andβ-catenin in tumor tissues from both transcription and protein levels.Besides,berberine also suppressed the protein expression of HNF4α,WNT5a andβ-catenin in liver tissues.CONCLUSION Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors,and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.

Inhibiting the expression of hepatocyte nuclear factor 4 alpha attenuates lipopolysaccharide/ D-galactosamine-induced fulminant hepatic failure in mice

BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.

Corticosteroid-induced bradycardia in multiple sclerosis and maturity-onset diabetes of the young due to hepatocyte nuclear factor 4-alpha mutation:A case report

BACKGROUND Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis(MS).Although steroid administration is generally welltolerated,cases of cardiac arrhythmia have been reported.Herein,we describe a young woman who developed marked sinus bradycardia and T-wave abnormalities after corticosteroid administration.We also present plausible explanations for the abnormalities observed in this patient.CASE SUMMARY An 18-year-old woman experienced vertiginous dizziness and binocular diplopia 1 wk prior to admission.Neurological examination revealed left internuclear ophthalmoplegia with left peripheral-type facial palsy.The initial laboratory results were consistent with those of type 2 diabetes.Brain magnetic resonance imaging revealed multifocal,non-enhancing,symptomatic lesions and multiple enhancing lesions.She was diagnosed with MS and maturity-onset diabetes of the young.Intravenous methylprednisolone was administered.On day 5 after methylprednisolone infusion,marked bradycardia with T-wave abnormalities were observed.Genetic evaluation to elucidate the underlying conditions revealed a hepatocyte nuclear factor 4-alpha(HNF4A)gene mutation.Steroid treatment was discontinued under suspicion of corticosteroid-induced bradycardia.Her electrocardiogram changes returned to normal without complications two days after steroid discontinuation.CONCLUSION Corticosteroid-induced bradycardia may have a significant clinical impact,especially in patients with comorbidities,such as HNF4A mutations.

Expression of hepatocyte nuclear factor 4 alpha,wingless-related integration site,andβ-catenin in clinical gastric cancer

BACKGROUND Gastric cancer(GC)is the second most common cause of cancer-related deaths worldwide.Hepatocyte nuclear factor 4 alpha(HNF4α)that belongs to the nuclear hormone receptor superfamily,is overexpressed in GC tissues,and might be involved in the development of GC by regulating its downstream winglessrelated integration site(WNT)/β-catenin signaling.AIM To clarify the expression of HNF4α/WNT5a/β-catenin signaling proteins in clinical GC tissues.METHODS We immunohistochemically stained pathological blocks of GC and matched paracancerous tissues.The intensity of HNF4α,WNT5a andβ-catenin staining in the tumor cells was determined according to cell rates and staining intensity.The correlations between GC and HNF4α,WNT5a,andβ-catenin expression using chisquare and paired chi-square tests.Relationships between double-positive HNF4αand WNT5a expression and types of gastric tumor tissues were assessed using regression analysis.Correlations between HNF4αand WNT5a expression at the RNA level in GC tissues found in the TCGA database were analyzed using Pearson correlation coefficients.RESULTS We found more abundant HNF4αand WNT5a proteins in GC,especially in mucinous adenocarcinoma and mixed GC than in adjacent tissues(P<0.001).Low and high levels of cytoplasmicβ-catenin respectively expressed in GC and adjacent tissues(P<0.001)were not significantly associated with pathological parameters.CONCLUSION The expressions of HNF4αand WNT5a could serve as early diagnostic biomarkers for GC.

Role of Hepatocyte Nuclear Factor 4α in Regulating Hepatic Differentiation and the Inflammatory Response in HCC

Limited treatment options are available for hepatocellular carcinoma(HCC),especially in the advanced stage,which is associated with a poor prognosis.Many studies have demonstrated that hepatocyte nuclear factor 4α(HNF 4α)plays an important role in hepatic differentiation and the carcinogenesis of HCC.HNF 4αcritically regulates hepatic differentiation by controlling a large number of genes involved in hepatic functions including metabolism,xenobiotic detoxification,bile acid synthesis,and serum protein production.It has also been confirmed to play an important role in the inflammatory environment in HCC.Thus,HNF 4αis considered to be a promising target for the treatment of HCC.Some studies have demonstrated that regulating HNF 4αexpression in HCC had beneficial effects in in vivo and in vitro experiments.We herein review the role of HNF 4αin regulating hepatic metabolism and the inflammatory response,aiming to provide some ideas on induced hepatic differentiation therapy and regulating the inflammatory microenvironment for the treatment of advanced HCC.

转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化

Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

Management of monogenic diabetes in pregnancy:A narrative review

Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.

HNF-4α determines hepatic differentiation of human mesenchymal stem cells from bone marrow

AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). METHODS: Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either re-verse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes. CONCLUSION: Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.

Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

The interplay between hepatocyte nuclear factor 4α(HNF4α)and cholesterol sulfotransferase(SULT2B1b)in hepatic energy homeostasis

The nuclear receptor hepatocyte nuclear factor 4alpha(HNF4α)plays a critical role in the regulation of metabolic homeostasis,including glucose homeostasis.Sulfotransferases(SULTs)catalyze the transfer of a sulfate group from 3-phosphoadenosine 5-phosphosulfate(PAPS)to an acceptor molecule.Sulfonation plays an essential role in regulating the chemical and functional homeostasis of endogenous and exogenous molecules.Among SULTs,the cholesterol sulfotransferase 2B1b(SULT2B1b)preferentially catalyzes the sulfoconjugation of cholesterol and oxysterols to form cholesterol sulfate and oxysterol sulfates.Hepatic gluconeogenesis represents a critical component of energy metabolism.Although there have been reviews on the regulation of glucose homeostasis by HNF4a,the interplay between HNF4a and SULT2B1b in hepatic glucose homeostasis remains scattered.In this review,we intend to provide an overview on how HNF4a functionally cross-talks with SULT2B1b to regulate hepatic glucose homeostasis and whether the HNF4a-SULT2B1b axis represents a novel therapeutic target for the management of metabolic liver disease and metabolic syndrome.

A Case Report of MODY_(3)Combined with Intestinal Neuroendocrine Tumor

Maturity-onset diabetes of the young 3(MODY_(3))is an autosomal dominant monogenic diabetes mellitus characterized by defective p-cell function and non-insulin-dependent early-onset diabetes mellitus.The facts that patients with MODY_(3) are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive,make its diagnosis very challenging.In this study,we reported a case of MODY_(3),which was verified to be caused by a mutation in hepatocyte nuclear factor 1αgene(c.598C>X p.Arg200Trp).In addition,the patient had a neuroendocrine tumor simultaneously,and a KMT2D gene mutation(c.5587C>G,p.Prol863Ala)might be associated with this leson.

Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum

This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(PAOA-flavone)-promoted small ubiquitin-related modifier(SUMO)modification in the atheroprotective efficacy of HNF1b.HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics,dual-luciferase reporter gene assay,and chromatin immunoprecipitation.HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages,leading to a depression in atherosclerotic plaque formation in low-density lipoprotein(LDL)receptor-deficient(LDLR−/−)mice.Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification.The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages.PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1(SAE1)expression and SAE1-catalyzed SUMOylation of the HNF1b protein,which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient(ApoE−/−)mice.Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration.In summary,HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis.This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated,SAE1-catalyzed SUMOylation of the HNF1b protein.

Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5

Objective There is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome （RCAD）/maturity onset diabetes of the young type 5 （MODY5）. The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominant TCF2 anomalies. Data sources MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification （hypomethylation and hypermethylation）, loci associated with cancer risk, and somatic TCF2 anomalies were all excluded. Study selection After searching the literature, 50 articles were selected. Results The detection rate of TCF2anomalies was 9.7% and varied considerably among MODY （1.4%）, renal structure anomalies （RSA） （21.4%） and RSA with MODY （41.2%） subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain： exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA （89.6%） and diabetes mellitus （DM） （45.0%）. However, the concurrence of RSA and DM was relatively low （27.5%）, which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients with TCF2 anomalies. Analysis of phenotypes of TCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function （IRF） and DM according to mutation type but not mutation location. Conclusion These valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.

Bile reflux and bile acids in the progression of gastric intestinal metaplasia

Gastric intestinal metaplasia(GIM)is a precancerous lesion of gastric cancer(GC)and is considered an irreversible point of progression for GC.Helicobacter pylori infection can cause GIM,but its eradication still does not reverse the process.Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa,and bile acids in refluxed fluid have been widely reported to be associated with GIM.This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor(PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha(HNF4 a)-glucose transporter 2(GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4 a expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4 a expression, while silencing PXR upregulated HNF4 a and GLUT2 expression.Silencing HNF4 a decreased GLUT2 expression, while overexpressing HNF4 a increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4 a reversed the atorvastatininduced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4 a mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4 a downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4 a plasmid increased Slc2 a2 promoter activity. Hnf4 a silencing or pregnenolone-16 a-carbonitrile(PCN) suppressed the Slc2 a2 promoter activity by decreasing HNF4 a recruitment to the Slc2 a2 promoter. Liver-specific Hnf4 a deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4 a and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4 aGLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Establishment and characterization of a new cell culture system for hepatitis B virus replication and infection

Hepatitis B virus(HBV)is a primary cause of chronic liver diseases in humans.HBV infection exhibits strict host and tissue tropism.HBV core promoter(Cp)drives transcription of pregenomic RNA(pg RNA)and plays a key role in the viral life cycle.Hepatocyte nuclear factor 4α(HNF4α)acts as a major transcriptional factor that stimulates Cp.In this work,we reported that BEL7404 cell line displayed a high efficiency of DNA transfection and high levels of HBV antigen expression after transfection of HBV replicons without prominent viral replication.The introduction of exogenous HNF4αand human sodium taurocholate cotransporting polypeptide(h NTCP)expression into BEL7404made it permissive for HBV replication and susceptible to HBV infection.BEL7404-derived cell lines with induced HBV permissiveness and susceptibility were constructed by stable co-transfection of h NTCP and Tet-inducible HNF4αfollowed by limiting dilution cloning.HBV replication in such cells was sensitive to inhibition by nucleotide analog tenofovir,while the infection was inhibited by HBV entry inhibitors.This cell culture system provides a new and additional tool for the study of HBV replication and infection as well as the characterization of antiviral agents.

Protection of Sophocarpine on Colonic Barrier in DSS-induced Acute Colitis in Mice by Increasing Expression of HNF4α

Objective To investigate the possible protective effects of sophocarpine on mucosal injury and epithelial barrier disruption on dextran sulfate sodium （DSS）-induced acute colitis. Methods Male BALB/c mice were randomly divided into three groups. The mice in normal group were given normal water, and those in model and sophocarpine- treated groups were given 2.5% DSS for 6 d to induce acute colitis. Sophocarpine （30 mg/kg） was ip administered once daily during the study period. Severity of colitis was evaluated by disease activity index （DAI）, histological injury and inflammatory cytokine production including tumor necrosis factor-α （TNF-α）, interleukin-lβ （IL-Iβ）, and monocyte chemoattractant protein-1 （MCP-1）. The colonic barrier disruption was assessed by testing the expression of junctional adhesion molecule-1 （JAM-1）, E-cadherin （E-CAD）, and desmocollin-2 （DSC-2） in colon mucosa. Expression of HNF4~ in colon mucosa was detected by immunohistochemistry staining and real-time RT-PCR, respectively. Results Compared with normal group, DAI, colonic shortening, and histopathological injury in model group were elevated （P 〈 0.05）, but reduced in sophocarpine-treated group （P 〈 0.05）. Compared with model group, the mRNA expression of inflammatory cytokines （TNF-α, IL-16, MCP-1） were obviously lower in sophocarpine-treated group （P 〈 0.05）, while the cellular junction proteins （E-CAD, JAM-l, and DSC-2） were higher （P 〈 0.05）. The expression of HNF4α at mRNA and protein levels was decreased significantly in model group, but increased apparently in sophocarpine-treated group. Conclusion Sophocarpine can enhance the expression of HNF4α, promote the expression of colonic intrecellular junctions, thus, maintain the integrity of the colonic barrier and inhibit the colitis process. We suggest that sophocarpine could enhance the production of cellular junction proteins to protect the intestinal barrier fuction, at least partly, in HNF4α-dependent pathway.