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Occludin is transmembrane protein and a key constituent of tight junction, and might participate in barrier function and fence function of epithelia and endothelia. It has been shown to be aberrantly expressed in malignant tumors and plays a role in carcinogenesis and tumor progression. The prognostic significance of Occludin expression has been implicated in various human cancers. However, the prognostic significance of Occludin expression in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we screened the tight junction genes aberrantly expressed based on two published gene microarray datasets (GSE20347 and GSE23400), and examined 95 esophageal cancer cases to assess immunohistochemical expression patterns of Occludin based on tissue array. Down-regulation of Occludin expression was shown in ESCC as compared with adjacent non-neoplastic specimens (P = 0.003). Decreased expression of Occludin was correlated with high histological grade (P = 0.017). Decreased expression of Occludin was also correlated with short overall survival (P = 0.014). The results indicated Loss of Occludin expression was associated with poor prognosis in ESCC, and Occludin expression was potentially a good predictor of prognosis in ESCC.

ObjectiveTo investigate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in the Tibet Autonomous Region, China.MethodsIn this cross-sectional study, a stratified random sampling method was used for collecting samples in the Tibet Autonomous Region. A total of 10,000 individuals were selected from October 2016 to June 2017. A previously-published, validated questionnaire including six items related to the symptoms of GERD was used for evaluating GERD. In addition, basic demographic data, lifestyle, dietary habits, medical history and family history of GERD were investigated to identify risk factors of GERD.ResultsA total of 5,680 completed questionnaires were collected and analyzed. The prevalence of GERD in this area was 10.8%. Age (30–40 years vs. under 18 years, odds ratio (OR): 3.025; 40–50 years vs. under 18 years, OR: 4.484), education level (high school vs. primary, OR: 0.698; university vs. primary, OR: 2.804), ethnic group (Han vs. Tibetan, OR: 0.230; others vs. Tibetan, OR: 0.304), altitude of residence (4.0–4.5 km vs. 2.5–3.0 km, OR: 2.469), length of residence (P< 0.05) and independently associated with GERD.ConclusionsThe prevalence of GERD is high in the Tibet Autonomous Region, China. Geographic conditions, ethnic group and lifestyle are risk factors for GERD.

Cyclooxygenase-2 (COX-2) inhibitor, celecoxib, causes growth inhibition of human gastric carcinoma cells, but it remains unclear whether celecoxib inhibits Helicobacter pylori-induced invasion of gastric cancer cells. The adenine nucleotide translocator (ANT) is a mitochondrial bi-functional protein. We speculate that ANT-dependent pathways might contribute to H. pylori-induced invasion and metastasis of gastric cancer cells. Therefore, in the present study, we evaluate the effect of celecoxib on H. pylori-induced gastric cancer cell motility and invasion. We also explore the role of ANTs in H. pylori-induced gastric cancer cell motility and invasion of gastric cancer cell line AGS. Our results demonstrate that celecoxib induces anoikis-like apoptosis and suppresses the proliferation and invasion of gastric cancer cells induced by H. pylori in culture. RT-PCR and Western blot analysis indicates that celecoxib upregulates the expression of ANT1 and ANT3; however, celecoxib did not increase the expression of ANT2. Our results suggest that celecoxib could be an effective means for suppressing proliferation and invasion of gastric cancer cells induced by H. pylori through an adenine nucleotide translocator-dependent mechanism.

Background and Aim Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. Methods A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. Results Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3–18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. Conclusions The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.

Summary Esophageal cancer is the eighth most common cancer and causes the sixth highest cancer-related mortality worldwide. The 5-year survival of patients suffering from esophageal cancer in either advanced stage or metastasis is less than 20%. MicroRNAs are small, well conserved, non-coding RNA molecules that either repress translation or promote mRNA degradation based on the degree of complementary between miRNAs and mRNAs. Based on biogenesis and function of microRNAs, specific microRNA profiles, either from cancerous tissues or serum, were able to serve as diagnostic and prognostic biomarkers of esophageal cancer and predicted the effectiveness of surgery and chemoradiotherapy. MicroRNAs could also influence the biological behaviors of esophageal cancer cells, such as cellular proliferation, apoptosis, invasion and metastasis. MicroRNAs were also associated with multi-drug resistance of esophageal cancer. Further studies on the roles of microRNAs in esophageal cancer would provide a strategy to prevent and treat esophageal cancer, and reverse multi-drug resistance of esophageal cancer.

With many advantages over other therapeutic agents such as monoclonal antibodies, aptamers have recently emerged as a novel and powerful class of ligands with excellent potential for diagnostic and therapeutic applications. Typically generated through Systematic Evolution of Ligands by EXponential enrichment (SELEX), aptamers have been selected against a wide range of targets such as proteins, phospholipids, sugars, nucleic acids, as well as whole cells. DNA/RNA aptamers are single-stranded DNA/RNA oligonucleotides (with a molecular weight of 5-40 kDa) that can fold into well-defined 3D structures and bind to their target molecules with high affinity and specificity. A number of strategies have been adopted to synthesize aptamers with enhanced in vitro/in vivo stability, aiming at potential therapeutic/diagnostic applications in the clinic. In cardiovascular diseases, aptamers can be developed into therapeutic agents as anti-thrombotics, anti-coagulants, among others. This review focuses on aptamers that were selected against various molecular targets involved in cardiovascular diseases: von Willebrand factor (vWF), thrombin, factor IX, phospholamban, P-selectin, platelet-derived growth factor, integrin α(v)β(3), CXCL10, vasopressin, among others. With continued effort in the development of aptamer-based therapeutics, aptamers will find their niches in cardiovascular diseases and significantly impact clinical patient management.

The following on progression to adenocarcinoma and markers of Barrett's esophagus includes commentariess on the expression of claudin 4 in Barrett's adenocarcinoma; the role of acid and bile salts; the role of insulin-like growth factor; the value of reactive oxygen species; the importance of abnormal methylation; genetic alterations in stromal cells and genomic changes in the epithelial cells; the value of confocal laser endomicroscopy for the subsurface analysis of the mucosa; indications for statins as adjuvant chemotherapeutic agent; the sequence of molecular events in malignant progression in Barrett's mucosa; and the value of the macroscopic markers and of p53 mutations.

The following on prevalence and incidence of adenocarcinomas in Barrett's esphophagus (BE) includes commentaries on the mechanisms of a potential protective effect of proton pump inhibitors (PPIs) on progression of BE to high-grade dysplasia; evaluation of the role of PPIs in decreasing the risk of degeneration; the geographical variations of incidence of BE; the role of the nonmorphologic biomarkers; the relationship between length of BE and development of cancer; the confounding factors in incidence rates of BE; the role of the increase of cell differentiation and apoptosis induced by PPIs in the diminution of cancer risk; the frequency of occult neoplastic foci and unsuspected invasive cancer in surgical specimens; the influence on the indications of endoscopic therapy; the overestimation of regression in surgical series; attempts to evaluate the reasons for variations of cancer incidence in the literature; and progress in screening and surveillance for BE.

The role of esophageal hypersensitivity in functional heartburn (FH) with negative pH test, negative symptom index, and the proton pump inhibitor (PPI) failure has not been established. The aim of this study was to investigate the characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with FH, nonerosive reflux disease, and erosive esophagitis and further characterize the pathophysiologic mechanism of FH.A total of 21 FH patients (with esophageal acid exposure3.1% and a symptom index50% and nonresponse to a therapeutic trial with proton pump inhibitors, 25 Nonerosive reflux disease (NERD) patients (with esophageal acid exposure4%), 23 erosive esophagitis (EE) patients (LA grade B to D), and 18 healthy controls were recruited in the study. Mechanosensitivity including the initial perception threshold (IPT) and pain threshold (PT) was evaluated by using a Barostat with a double-random staircase distension protocol. Chemosensitivity was graded along a visual analog scale after perfusion of saline and 0.1 N HCl.The baseline IPTs and PTs were all lower in patients with FH, NERD, and EE than in the controls (all P0.01). In addition, the baseline PT in FH patients was significantly lower than those in NERD (P=0.015) and EE patients (P0.001). After acid perfusion, the mean symptom intensity scores were significantly greater in patients with FH, NERD, and EE than those in the controls (all P0.001). The postacid perfusion IPTs in patients with FH, NERD, and EE were all significantly lower than the corresponding baseline values (all P0.01). The PTs in FH (P=0.026) and EE patients (P0.001) were significantly lower than the corresponding baseline values. Moreover, the postacid perfusion PT was significantly lower in FH patients than in NERD patients (P0.001).FH patients are more sensitive to mechanical or chemical stimuli than NERD patients. Sensitization of esophageal acid-sensitive chemoreceptors may exert a significant influence on the pressure-sensitive mechanoreceptors, and there is the cooperative interaction in the process of esophageal visceral hyperalgesia.

In previous works, we showed by transient expression studies in COS-1 cells that the C-terminal domain of rat intestinal membrane mucin (rMuc3) that was cloned in the pSecTag2 plasmid (named as p20) is posttranslationally cleaved twice. One location is between the glycine and the serine within a LS1KGS2IV1V2 motif, and the other is in the 49 kDa membrane-tethered fragment at an undefined site. The sea-urchin sperm protein, enterokinase and agrin module of rMuc3 is responsible for the cleavage and association of the cleaved fragments. The present study demonstrates how the conservative cleavage motif LS1KGS2IV1V2 contributes to posttranslational processing through mutagenesis of each residue in the LS(1)KGS2IV1V2 motif. Mutation of S2 to alanine (p20s2/a) completely prevented cleavage. While p20k/a (in this construct the K is replaced by A) and p20s1/a (in this construct the S1 is replaced by A) (6 and 3%) showed almost the same result as the wild-type p20 transfectant (4%), 79, 39, 22, 17, and 14% of the products from p20g/a (in this construct the G is replaced by A), p20i/a (in this construct the I is replaced by A), p20l/a (in this construct the L is replaced by A), p20v2/a (in this construct the V2 is replaced by A), and p20v1/a (in this construct the V1 is replaced by A) remained uncleaved. The cleaved N-terminal fragment of the p20s1/a transfectant was 26 kDa, but the N-terminal fragments from p20, p20g/a, p20l/a, p20k/a, p20i/a, p20v1/a, and p20v2/a were 30 kDa. The S1 residue was possibly O-glycosylated, which was supported by deglycosylation with O-cocktail (a mixture of glycosidases). The N-terminal fragment of p20s1/a transfected cells was present at high levels in the spent media. Thus, the S2, G, I, L, V2, and V1 residues within the conserved cleavage motif, LS1KGS2IV1V2, are important for cleavage and contribute to the structural formation and conformational stress of the small loop between the beta2 and the beta3 strands. The S1 residue is possibly O-glycosylated, and mutation of S1 residue to alanine does not affect the cleavage of the LS1KGS2IV1V2 motif, but it is important for the dissociation and further release of the cleaved N-terminal fragment from the cell surface.

The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 +/- 0.97 to 0.80 +/- 0.47 after 8 weeks (P < 0.001 versus control). The endoscopic inflammation score in rebamipide group also decreased from 2.65 +/- 0.09 to 0.60 +/- 0.10, which showed better effects than sucralfate. It was shown a significant improvement (P < 0.01) in prostaglandin E2 (PGE(2)) contents in rebamipide-treated subjects mucosa (225.4 +/- 18.3 pg/g versus 266.7 +/- 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG.

Many epidemiological studies have recently been published on acute pancreatitis; however, there is no known published report on pancreatitis in China. The present study aims to assess the etiology and mortality of severe acute pancreatitis in China.Fifteen medical centers located throughout mainland China were involved in this retrospective study. The medical records of 1976 patients, who were admitted to these centers with the diagnosis of severe acute pancreatitis from December 1990 to December 2005, were reviewed. Epidemiological, laboratory, radiological, and therapeutic data for each case were collected on a standardized form for analysis. Severity of pancreatitis was graded according to established criteria.Of the 1976 patients (1028 men, 948 women; mean age, 56.2 +/- 16.5 years; range, 9-94 years). Biliary tract disease (58.7%) was the main etiologic factor, whereas in 25.2%, the cause was identified as idiopathic. Endotherapy was performed in 9.1% of the severe biliary cases, but only in 33%, it was performed within 72 hours. The mean duration of hospitalization was 22.5 +/- 21.4 days, and the overall mortality rate was 11.8%.In this retrospective study, biliary tract disease was the main etiologic factor of severe acute pancreatitis in China. The highest mortality occurred in severe idiopathic pancreatitis, and there was no clear relationship between mortality and age.

Esophageal squamous cell carcinoma is a common digestive tract cancer with poor prognosis. Nucleostemin is a nucleolar protein expressed in stem and cancer cells, involved in the regulation of cell proliferation. p21 plays an important role in negative regulation of the cell-cycle. We investigated the role of nucleostemin through regulating p21 expression in the occurrence and progression of human esophageal carcinoma.The expression of nucleostemin and p21 protein and of nucleostemin was knocked-down by means of RNA interference (RNAi) in Eca109 cells. Then, mRNA and protein expressions of nucleostemin and p21 were determined by reverse transcriptase polymerase chain reaction and Western blotting, respectively. In addition, the effect of nucleostemin RNAi on cell proliferation and cell cycle distribution of Eca109 cells were observed.Nucleostemin was high expressed, but p21 was low expressed in esophageal carcinoma tissues while increased level of nucleostemin protein was associated with reduced p21. inhibition of nucleostemin resulted in an increased expression of p21 and inhibition of cell proliferation, cause G1/G0 phase cells increased and S-phase cells reduced greatly in Eca109 cells.Silence of nucleostemin inhibit cell proliferation through up-regulating p21 expression and nucleostemin may be involved in the pathogenesis of esophageal squamous cell carcinoma.

Oesophageal visceral hypersensitivity is thought to be important in generating symptoms in functional heartburn (FH). However, the neurophysiological mechanisms involved are poorly understood. The aim of this study was to compare the characteristics of oesophageal cortical evoked potentials (CEPs) induced by balloon distension and acid perfusion in FH and controls. We studied 21 FH patients and 12 healthy volunteers. Oesophageal mechanical stimulation was performed using the specially constructed mechanical pump. CEPs were recorded using the 10-20 international system of electroencephalogram recording. Oesophageal distention elicited recognizable, reproducible and muti-peak CEPs. CEP latencies for N1, P1 and N2 components were significantly shorter (P = 0.016, P = 0.003 and P = 0.031, respectively) in FH than in controls before perfusion. Acid perfusion significantly decreased the latencies of N1, P1 and N2 (P = 0.022, P = 0.007 and P = 0.041, respectively) and significantly increased the amplitude of P1-N2 components (P = 0.020) in FH patients, but not in controls. In conclusion, cortical evoked potential responses evoked by oesophageal distention and acid perfusion were greater in FH than in controls, suggesting that dysfunction of visceral neural pathways and/or alterations in cortical processing may produce and mediate oesophageal hypersensitivity in FH. These findings provide the evidence that central sensitization contributes to the development and maintenance of oesophageal hypersensitivity.

Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China.A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure.Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3-18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8.The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.

The following on progression to adenocarcinoma and markers of Barrett's esophagus includes commentariess on the expression of claudin 4 in Barrett's adenocarcinoma; the role of acid and bile salts; the role of insulin-like growth factor; the value of reactive oxygen species; the importance of abnormal methylation; genetic alterations in stromal cells and genomic changes in the epithelial cells; the value of confocal laser endomicroscopy for the subsurface analysis of the mucosa; indications for statins as adjuvant chemotherapeutic agent; the sequence of molecular events in malignant progression in Barrett's mucosa; and the value of the macroscopic markers and of p53 mutations.

The following on prevalence and incidence of adenocarcinomas in Barrett's esphophagus (BE) includes commentaries on the mechanisms of a potential protective effect of proton pump inhibitors (PPIs) on progression of BE to high-grade dysplasia; evaluation of the role of PPIs in decreasing the risk of degeneration; the geographical variations of incidence of BE; the role of the nonmorphologic biomarkers; the relationship between length of BE and development of cancer; the confounding factors in incidence rates of BE; the role of the increase of cell differentiation and apoptosis induced by PPIs in the diminution of cancer risk; the frequency of occult neoplastic foci and unsuspected invasive cancer in surgical specimens; the influence on the indications of endoscopic therapy; the overestimation of regression in surgical series; attempts to evaluate the reasons for variations of cancer incidence in the literature; and progress in screening and surveillance for BE.

IgGFcgammaBP and TFF3 are related with adaptation during injury, mucosal defense, and epithelial healing. In this work, we produced the polyclonal antibodies for rat IgGFcgammaBP or TFF3 and assessed their tissue distributions in adult and prenatal rats, rTFF3 molecular patterns under reduced and nonreduced condition, involvement of IgGFcgammaBP, and TFF3 in dextran sulfate sodium (DSS)-induced colitis. Polyclonal antibodies of rat IgGFcgammaBP or TFF3 were produced with their synthetic polypeptide. Rat TFF3 was detected in the scraped intestinal mucosa by SDS/PAGE and Western blotting. Immunohistochemical stainings of rat IgGFcgammaBP or TFF3 were performed in different tissues, mainly in mucin-producing tissues, of adult rat and prenatal rat intestine. Rat IgGFcgammaBP and TFF3 were immunohistochemically detected in the distal colon of rat colitis model induced with 7% DSS. IgGFcgammaBP and TFF3 were mainly expressed in the intestinal mucosa with different distribution patterns. The scattered staining was also found in the epithelium of bile duct. There was strong expression of IgGFcgammaBP and TFF3 in rat embryonic intestine. There were two kinds of rTFF3 complexes existed with different molecular weights, 250 and 55 kDa, under nonreduced conditions, but shifted to 6 kDa under reduced conditions. In the DSS-induced colitis model, IgGFcgammaBP and TFF3 were significantly decreased in the distal colon mucosa at the onset and active phases comparing with the normal control, partially recovered at the regenerative phase. Based on these findings,IgGFcgammaBP and TFF3 were widely expressed in the intestinal mucosa, depleted during DSS-induced colitis. Rat TFF3 existed mainly in two complexes with 250 and 55 kDa molecular weights. The present findings indicate they are two important goblet cell-derived components possibly related to the pathogenesis of DSS-induced colitis, a rat model of ulcerative colitis.

To investigate the change in the expression of E-Cadherin of human hepatocarcinoma cell line SMMC-7721 after transfection by antisense human DNA MTase gene.DNA MTase gene eukaryotic expression vectors, including sense and antisense fragments, were constructed with recombinant technology and transfected into the hepatocarcinoma cell line SMMC-7721 with liposome DOTAP. The expression of DNA MTase gene mRNA and E-Cadherin gene mRNA was examined with RT-PCR and the expression of E-Cadherin with immunohistochemical and flow cytometry. The status of methylation in E-Cadherin gene promoter area was examined with methylation specific PCR (MSP).The sense and antisense eukaryotic expression vectors were successfully constructed and then the constructed recombinant plasmids were successfully transfected into SMMC-7721 cell with liposome DOTAP. The expression of endogenous DNA MTase mRNA was obviously decreased with E-Cadherin gene mRNA and its activity increased in the SMMC-7721 cell, which was tranfected with antisense DNA MTase gene fragment. Moreover, demethylation in the promoter area of E-Cadherin gene was observed with MSP.Demethylation in the promoter area and increasing mRNA level of E-Cadherin gene can be induced by expression inhibition of DNA MTase gene of SMMC-7721 cell line.

To explore the effect of antisense gene to human telomerase reverse transcriptase (hTRT) on reversing malignant phenotypes of liver cancer cell lines.Sense and antisense eukaryotic expressing vector of hTRT gene was transfected into human liver cancer line HepG(2) with the DOTAP liposomal transfection method. Changes of cellular malignant phenotypes through proliferation capacity, telomerase activity, cloning formation in soft agar, invasive capacity in Borden's chamber model and tumorigenicity in nude mice were examined.Sense and antisense eukaryotic expressing vector was successfully transfected into HepG(2). The obtained transfectants termed HepG(2)-sense (HepG(2)-S) and HepG(2)-antisense (HepG(2)-AS) stably produced sense and antisense hTRT, respectively. HepG(2)-AS showed an obvious decrease in growth and telomerase activity. HepG(2)-AS penetrated cells through Matrigel were decreased significantly compared with HepG(2) and HepG(2)-S. Cloning efficiency in soft agar and tumorigenicity in nude mice was also markedly inhibited in HepG(2)-AS.Antisense gene to hTRT can significantly suppress cancer cell growth, partially reverse malignant phenotypes of HepG(2), which indicates that hTRT may be a new target gene for antisense gene therapy of liver cancer.

Hepatopoietin (HPO) is a novel polypeptide mitogen specific for hepatocytes and hepatoma cell lines, which is derived from liver and supports its regeneration. To determine whether HPO acts via a receptor-based signal transduction, recombinant human hepatopoietin was labeled by iodination and used to characterize its binding activity by specific displacement test and Scatchard analysis in primarily cultured rat hepatocytes and human hepatoma Hep-G2 cells. The binding was saturable and specific because it was replaceable by HPO but not by epidermal growth factor, transforming growth factor-α, or insulin. Scatchard analysis indicated the presence of a single class of high affinity receptor with dissociation constant (K d) of 2 and 0.7 pm, and a receptor density of about 10,000 sites/cell and 55,000 sites/cell in the rat hepatocytes and human hepatoma cells, respectively. TheK d values were consistent with the half-maximum dose of HPO activity. Affinity cross-linking of the receptor with125I-HPO revealed a polypeptide of molecular mass approximately 90 kDa by SDS-polyacrylamide gel electrophoresis. Thus, the molecular mass of the HPO receptor was calculated to be about 75 kDa. These data demonstrated the existence of an HPO receptor in hepatocytes and hepatoma cells, which may account for biological effect.