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Biomedical subjects

Nobuhiro Sato

Publications and source records attributed to Nobuhiro Sato.

At least 19 recordsLinked to original sources
PubMed2006

Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat.

BACKGROUND/AIMS: In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat. METHODS: Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1ml/kg, twice per week) and dalteparin (50IU/kg, daily) for 7 weeks. RESULTS: Dalteparin did not prevent acute CCl4-induced hepatic necrosis and elevation in serum aminotransferases levels; however, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were dramatically increased 24h after simultaneous administration of CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-induction of smooth muscle alpha-actin expression, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels in the liver. Further, dalteparin blunted platelet-derived growth factor (PDGF)-induced increases in 5-bromo-2'deoxyuridine (BrdU) uptake in 3-day cultured hepatic stellate cells (HSCs) in a dose-dependent manner. CONCLUSIONS: Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation.

Actins↗
PubMed2006

Exacerbation of dietary steatohepatitis and fibrosis in obese, diabetic KK-A(y) mice.

In this study, we investigated a dietary model of steatohepatitis caused by methionine- and choline-deficiency (MCD) in obese, diabetic KK-A(y) mice. Male KK-A(y) mice and C57Bl/6 mice were fed an MCD diet for up to 8 weeks, and liver pathology was evaluated. Hepatic steatosis and inflammatory infiltration were more prominent in KK-A(y) mice than in C57Bl/6 mice 4 weeks after feeding with MCD diet. MCD diet-induced increases in tumor necrosis factor (TNF)-alpha mRNA levels, as well as lipid peroxidation, in the liver were also potentiated significantly in KK-A(y) mice. Extended degree of hepatic fibrosis was observed in KK-A(y) mice as compared to C57Bl/6 mice 8 weeks after feeding with MCD diet. Indeed, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels were significantly higher in KK-A(y) mice following dietary treatment. Serum adiponectin levels were elevated nearly two-fold when C57Bl/6 mice were given MCD diet for 4 weeks; however, serum adiponectin levels in KK-A(y) mice fed both the control- and MCD diet were the same, reaching the values almost 1/2 of those in C57Bl/6 mice. In conclusion, KK-A(y) mice exhibit increased susceptibility to MCD diet-induced steatohepatitis, where hypoadiponectinemia most likely plays a key role in exacerbation of both inflammatory and profibrogenic responses.

Journal Article↗
PubMed2006

Coexistence of esophageal superficial carcinoma and multiple leiomyomas: A case report.

Leiomyomas are the most common benign tumors of the esophagus. They usually occur as a single lesion or as two or three nodules. Only two cases of esophageal multiple leiomyomas comprising more than 10 nodules have been reported previously. Moreover, there have been few reports of esophageal squamous cell carcinoma overlying submucosal tumors. We describe a 71-year-old man who was diagnosed as having a superficial esophageal cancer coexisting with two or three leiomyoma nodules. During surgery, 10 or more nodules that had not been evident preoperatively were palpable in the submucosal and muscular layers throughout the esophagus. As intramural metastasis of the esophageal cancer was suspected, we considered additional lymphadenectomy, but had to rule out this option because of the patient's severe anoxemia. Microscopic examination revealed that all the nodules were leiomyomas (20 lesions, up to 3 cm in diameter), and that invasion of the carcinoma cells was limited to the submucosal layer overlying a relatively large leiomyoma. This is the first report of superficial esophageal cancer coexisting with numerous solitary leiomyomas. Multiple minute leiomyomas are often misdiagnosed as intramural metastasis, and a leiomyoma at the base of a carcinoma lesion can also be misdiagnosed as tumor invasion. The present case shows that accurate diagnosis is required for the management of patients with coexisting superficial esophageal cancer and multiple leiomyomas.

Aged↗
PubMed2006

Hepatic steatosis is a predictor of poor response to interferon alpha-2b and ribavirin combination therapy in Japanese patients with chronic hepatitis C.

In this study, we evaluated whether hepatic steatosis affects the viral response to interferon (IFN) and ribavirin combination therapy in Japanese patients with chronic hepatitis C (CHC). Eighty CHC patients treated with IFN alpha-2b and ribavirin for 24 weeks were evaluated retrospectively. Liver biopsy specimens were assessed histopathologically, and grade of steatosis was scored as follows: grade 0: <5%; grade 1: 5-33%; grade 2: 33-66%; grade 3: >66%. Sustained viral response (SVR) was defined as negative for HCV-RNA by high-sensitivity qualitative reverse transcription-polymerase chain reaction (RT-PCR) at 24 weeks post-treatment. Hepatic steatosis graded 2 and higher was seen in 28.8% patients, whose average BMI were significantly higher than those in grade 0 patients. Grade of steatosis was well correlated with elevation in serum aminotransferases and gamma-glutamyltranspeptidase (gamma-GTP) levels, but not with histological degree of inflammation and fibrosis. The SVR rates were significantly lower in the group with overt steatosis (grade 2/3) as compared to the group with less steatosis (grade 0/1), the values being 30.4% and 57.9%, respectively. Moreover, grade of steatosis was selected as an independent negative factor for SVR in multivariate analysis. In conclusion, hepatic steatosis is an important predictor of poor response to therapy of IFNalpha-2b and ribavirin in patients with CHC.

Journal Article↗
PubMed2006

Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: Role of intracellular calcium and nitric oxide.

In alcoholic liver disease, ethanol-induced damage to sinusoidal endothelial cells (SECs) appears to be important in the progression of liver damage. However, little is known about the mechanisms responsible for protection of SECs against ethanol-induced injury. To elucidate the role of sphingosine 1-phosphate (S1P), which is stored in platelets and may be released from them on their activation, we investigated the effect of S1P on rat liver SECs in primary culture. Pretreatment of cells with 1 mumol/L S1P attenuated ethanol-induced apoptosis. Electron microscopy confirmed this protective effect of S1P on damaged SECs in liver tissues after perfusion of ethanol. In the absence of ethanol, S1P increased DNA synthesis as determined via incorporation of bromodeoxyuridine. S1P also ameliorated the decreased DNA synthesis of cells induced by ethanol. Addition of S1P to cells induced an increase in intracellular calcium concentrations and NO production in cells. Western blotting revealed that S1P significantly induced the activation of endothelial NO synthase (eNOS), but not Akt, and that S1P-induced activation of eNOS was blocked by trifluoperazine, a calmodulin inhibitor. Furthermore, N(G)-nitro-L-arginine methyl ester, a NO synthase inhibitor, cancelled the effect of S1P on DNA synthesis, apoptosis, and NO production in vitro as well as the protective effect of S1P on cell damage in situ. In conclusion, the biological effect of S1P is at least partially mediated by Ca(2+)-sensitive eNOS activation and subsequent NO formation; extracellular S1P could contribute to sinusoidal protection and remodeling in alcoholic liver injury.

Animals↗
PubMed2006

Clinicopathological features of nonpolypoid colorectal tumors as viewed from the patients' background.

BACKGROUND: This study was performed to characterize the clinicopathological features of colorectal tumors with flat-, depressed-, or protruded-type morphology (hereafter referred to simply as flat, depressed, or protruded lesions). METHODS: There are two major types of colorectal tumor: polypoid (protruded) and nonpolypoid (flat and depressed). A total of 130 lesions from 130 patients with colorectal submucosal invasive cancer were classified into three groups according to their macromorphology seen during endoscopy: flat (laterally spreading) and depressed nonpolypoid tumors and protruded polypoid tumors. The following factors in the patients' background were evaluated: indication for colonoscopy, age, and family history of colorectal cancer in first-degree relatives (i.e., parents, siblings, children). We also compared the following characteristics of the tumors: size, location, depth of submucosal invasion, vascular invasion, and frequency of synchronous and metachronous tumor lesions. RESULTS: The incidence of abnormal findings on follow-up studies after polypectomy as an indication for colonoscopy was significantly higher among patients with flat lesions (4/24, 16.7%) and depressed lesions (3/22, 13.6%) than among those with protruded lesions (1/84, 1.2%) (P < 0.01, P < 0.01). Patients with flat lesions (65.8 +/- 7.6 years old) were significantly older than those with protruded lesions (P < 0.05). The patients with flat tumors had a significantly higher rate of a family history of colorectal cancer (6/24, 25.0%) than patients with protruded or depressed lesions (P < 0.01, P < 0.05). The protruded lesions were significantly larger than the depressed lesions (size 13.3 +/- 6.7 mm) (P < 0.05), and the flat lesions (24.1 +/- 10.1 mm) were significantly larger than either the protruded or depressed lesions (P < 0.01, P < 0.01). Seventy-five percent (18/24) of the flat lesions were located in the right colon, and this proportion was significantly higher than that among the protruded or depressed lesions (P < 0.01, P < 0.01). The mean +/- SD depth of submucosal invasion was 1218 +/- 1034 microm in the flat lesions, 2392 +/- 1869 microm in the depressed lesions, and 2761 +/- 1929 microm in the protruded lesions, representing a significant difference (P < 0.05, P < 0.0001). Of the 24 patients with flat lesions, 9 (37.5%) showed vascular invasion; this proportion was significantly lower than that among patients with the depressed or protruded lesions (P < 0.01, P < 0.01). Patients with depressed lesions tended to have higher incidence of synchronous and metachronous malignant polyps than those with protruded or flat lesions. CONCLUSION: It is important to examine the morphology of colorectal tumors when diagnosing them and planning the treatment strategy, including follow-up, after resection of nonpolypoid tumors. It is useful to know the patient's family history so nonpolypoid tumors can be accurately diagnosed.

Aged↗
PubMed2006

Location of early colorectal cancers at fold-top may reduce the risk of lymph node metastasis.

PURPOSE: This study was designed to look for significant correlations between location of early colorectal cancer, distance from muscularis mucosae to muscularis propria, and the frequency of lymph node metastasis. METHODS: A total of 166 early colorectal cancers, including 67 surgically resected lesions, were evaluated. The cancers were divided into two groups: metastatic and nonmetastatic. Cancer lesions were further subtyped at the fold-top or fold-bottom. Macroscopic classifications and histology were performed. Absolute invasive depth and distance from muscularis mucosae to muscularis propria was measured. Multivariate analysis was used to assess relationships among the variables. RESULTS: The percentage of polypoid cancer lesions at fold-bottom was higher than at fold-top (74.5 vs. 51.8 percent), whereas flat-type cancer lesions at fold-bottom occurred less often than at fold-top (8.2 vs. 30.4 percent). Logistic regression showed that deep absolute invasive depth, lymphatic and vessel invasion, and cancer location (at fold-bottom) were the significant risk factors for early colorectal cancers leading to lymph-node metastasis. The distance from muscularis mucosae to muscularis propria with lymph-node metastasis (1,396.7 +/- 728.4 microm) was shorter than without lymph-node metastasis (3,533.9 +/- 2,507.8 microm; P < 0.01). Multivariate analysis showed that distance from muscularis mucosae to muscularis propria was a statistically significant factor for early colorectal cancers leading to lymph node metastasis (P = 0.0054). CONCLUSIONS: We conclude that early colorectal cancers at the fold-top or with a long distance from muscularis mucosae to muscularis propria have less tendency to metastasize to lymph nodes. Clinically, these results provide evidence of a new indicator of endoscopic mucosal resection for early colorectal cancers at the fold-top.

Colorectal Neoplasms↗
PubMed2006

Effect of low-molecular-weight heparin on the commitment of bone marrow cells to liver sinusoidal endothelial cells in CCl(4)-induced liver injury.

BACKGROUND/AIMS: Recently liver regeneration by bone marrow transplantation has been proposed as an alternative source of functional liver cells. We investigate commitment of bone marrow cells (BMCs) to liver regeneration and the effect of dalteparin sodium (DS) on regeneration of the damaged liver caused by carbon tetrachloride (CCl(4)) administration in the mice. METHODS: Liver injury was produced in 8-week-old mice by treating with CCl(4) for 4 weeks. Thereafter, mice received a lethal dose of irradiation (10Gy) to whole body, followed by injection of 1x10(7) green fluorescent protein (GFP)-positive BMCs via the tail vein. DS (50IU/kg, intraperitoneally) was administered daily for 28 consecutive days starting at 1 day post-BMC transplantation. Lineage marker analysis of GFP-positive liver cells was performed immunostaining with a CD31 antibody. RESULT: Four weeks after BMC transplantation, GFP-positive cells in the CCl(4)-damaged liver could be detected in the lobule displaying a meshwork architecture extending from the periportal to pericentral regions, a pattern simulating sinusoidal lining. This localization of GFP-positive cells suggested that these cells were closely associated with sinusoidal endothelial cells. By staining the GFP-positive cells for CD31, it was confirmed that the majority of the GFP-positive cells are also positive for CD31. The GFP(+)CD31(+) cells were barely detected in the control group (1.0+/-1.2 per field). In marked contrast, a numerous number of GFP(+)CD31(+) cells were detected in the liver section obtained from the CCl(4)-induced liver damage group (3.8+/-1.3 per field, P<0.05 versus control). The number of GFP(+)CD31(+) cells in CCl(4) plus DS-treated group was further increased to 8.3+/-1.3 per field (P<0.05 versus CCl(4)-induced liver damage group). CONCLUSION: The majority of GFP-positive BMCs was committed to sinusoidal endothelial cells. DS promoted BMC differentiation into sinusoidal endothelial cells in the CCl(4)-damaged liver.

Journal Article↗
PubMed2006

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

BACKGROUND AND AIM: Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. METHODS: In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. RESULTS: Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). CONCLUSIONS: Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.

Adult↗
PubMed2006

Endotoxin adsorption therapy for septic shock using polymyxin B-immobilized fibers (PMX): evaluation by high-sensitivity endotoxin assay and measurement of the cytokine production capacity.

Because of its low sensitivity, the conventional measurement method for endotoxin (ET) is not the most appropriate for monitoring the effect of ET adsorption therapy. Thus, the efficacy of ET adsorption therapy was investigated using a newly developed high-sensitivity ET assay method. The changes in the cytokine production capacity of whole blood were also examined. We treated 24 peritonitis patients who had developed postoperative septic shock with ET adsorption therapy using a column of polymyxin B-immobilized fibers (PMX) and their serum ET levels were measured using the high-sensitivity ET assay based on the kinetic turbidimetric Limulus assay. In addition, the changes in the tumor necrosis factor-(TNF-alpha) production capacity of whole blood following lipopolysaccharide (LPS) stimulation and clinical outcome in the study patients were also examined. The 28-day mortality rate was 12%. PMX-direct hemoperfusion (PMX-DHP) was associated with elevation of the mean arterial pressure and urine output, reduction in the mean dose requirement of vasopressor agents, and recovery from the shock state in all the patients. The PaO2/FIO2 ratio also showed significant improvement. Using the high-sensitivity ET assay, ET was detected in the blood of 20 out of the 24 patients (80%) before the PMX-DHP, and a significant reduction in the ET level was noted after the PMX-DHP. The TNF-alpha production capacity of whole blood, which was found to be lower in the septic shock patients than in healthy subjects, was significantly increased after PMX-DHP. Elimination of ET by PMX-DHP in septic shock patients was confirmed by the high-sensitivity ET assay. PMX-DHP is thus considered to be a useful adjuvant therapeutic technique in the treatment of septic shock. Also, PMX-DHP might alleviate the immunosuppression associated with severe sepsis.

Adsorption↗
PubMed2006

[Adipokine interrelationship with the liver].

Recent progress in adipocyte biology delineates that adipocytes not only store excess energy, but also respond to metabolic signals by secreting proteins that exert local, central, and peripheral effects. Among these adipokines are free fatty acids, plasminogen activator inhibitor-1, angiotensinogen, TNFa, leptin and adiponectin. Dysregulation of production of these adipokines and/or imbalance of their actions lead to a wide array of liver and systemic pathophysiology related to NASH such as 1) development of systemic and hepatic insulin resistance, 2) progression from benign fatty liver to steatohepatitis and 3) activation of hepatic fibrogenesis. This review deals with the emerging concept of the adipokine interrelationship with the liver.

Adipocytes↗
PubMed2005

Hard protective waterproof coating for high-power laser optical elements.

We developed a new method for making a waterproof coating by photooxidation of silicone oil. The silicone oil was spin coated onto the surfaces of optical elements, i.e., a plastic lens, a laser mirror, and a nonlinear optical crystal, and then irradiated with a xenon excimer lamp in air, which transformed the organic silicone oil into an amorphous glass film. This technique has enabled an optical thin film to transmit ultraviolet rays of wavelengths below 200 nm and to exhibit the characteristics of homogeneity, high density, and resistance to environmental effects and to corrosion by water, and a Mohs scale value of 5.

Journal Article↗
PubMed2005

The role of leptin in progression of non-alcoholic fatty liver disease.

Since non-alchoholic steatohepatitis (NASH) is often accompanied with metabolic syndrome comprising obesity, type-2 diabetes and hypertension, it is hypothesized that adipocytokines, insulin resistance and autonomic nervous system play crucial roles in disease progression of NASH. On the other hand, hepatic stellate cells (HSCs) have been shown to produce leptin when they get activated during hepatic fibrogenesis. Therefore, we investigated the role of leptin in fibrogenesis in the liver. Xenobiotics-induced liver fibrosis was extremely diminished in ob/ob mice and Zucker (fa/fa) rats, an inborn leptin- and leptin receptor (Ob-R)-deficient animal, respectively. Further, leptin increased transforming growth factor (TGF)-beta mRNA in isolated sinusoidal endothelial cells and Kupffer cells, suggesting that leptin promotes hepatic fibrogenesis through up-regulation of TGF-beta in the liver. Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. Taken together, it is postulated that leptin acts as a profibrogenic cytokine in sinusoidal microenvironment. These findings indicate that leptin is one of the key regulators for inflammation and progression of fibrosis in various chronic liver diseases including NASH.

Journal Article↗
PubMed2005

Conformational transition of the core chain in radiation-modified polysilane micelles formed in selective solvents.

Poly(methyl acrylate)-grafted poly(methyl-n-propylsilane) (PMPrS-g-PMA) and poly(acrylic acid)-grafted PMPrS (PMPrS-g-PAA) were synthesized by gamma-ray-induced graft polymerization, and the association behavior of these graft copolymers was investigated in selective solvents composed of good and poor solvents for the PMPrS main chain. Fluorescence spectroscopy with perylene as a fluorescent probe revealed that PMPrS-g-PAA in a water/THF mixed solvent self-assembles into micelles with a swollen core of PMPrS chains in the water content range of 50-95%. UV spectroscopy demonstrated that a further increase of the water content gives rise to the conformational transition of the PMPrS chains in the micelle core from the random conformation to the conformation that corresponds to that in the solid state at a water content of ca. 95%, independent of the grafting yield. Similar behavior was also observed in DMSO/THF solutions of PMPrS-g-PMA, for which the conformational transition occurred at the constant DMSO content of ca. 95%. These results indicate that solvatochromic behavior of polysilane, which is a characteristic feature of polysilane, proved to provide information on the inner structure of those micelles: PMPrS chains in the core undergo conformational transition as the content of the poor solvents for PMPrS increases, while maintaining the micelle structure.

Journal Article↗
PubMed2005

SMAD and p38 MAPK signaling pathways independently regulate alpha1(I) collagen gene expression in unstimulated and transforming growth factor-beta-stimulated hepatic stellate cells.

The hepatic stellate cell (HSC) is the predominant cell type responsible for excess collagen deposition during liver fibrosis. Both transforming growth factor-beta (TGF-beta), the most potent fibrogenic cytokine for HSCs, which classically activates Smad signaling, and p38 MAPK signaling have been shown to influence collagen gene expression; however, the relative contribution and mechanisms that these two signaling pathways have in regulating collagen gene expression have not been investigated. The aim of this study was to investigate the relative roles and mechanisms of both Smad and p38 MAPK signaling in alpha1(I) collagen gene expression in HSCs. Inhibiting either p38 MAPK or Smad signaling reduced alpha1(I) collagen mRNA expression in untreated or TGF-beta-treated HSCs, and when both signaling pathways were simultaneously inhibited, alpha1(I) collagen gene expression was essentially blocked. Both signaling pathways were found to independently and additively increase alpha1(I) collagen gene expression by transcriptional mechanisms. TGF-beta treatment increased alpha1(I) collagen mRNA half-life, mediated by increased stability of alpha1(I) collagen mRNA through p38 MAPK signaling but not through Smad signaling. In conclusion, both p38 MAPK and Smad signaling independently and additively regulate alpha1(I) collagen gene expression by transcriptional activation, whereas p38 MAPK and not Smad signaling increased alpha1(I) collagen mRNA stability.

Adenoviridae↗
PubMed2005

Severe dysplasia of the gallbladder associated with occult pancreatobiliary reflux.

Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary maljunction and can be associated with the occurrence of gallbladder carcinoma. We present the case of a patient with pancreatobiliary reflux despite having a normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom the resected gallbladder presented severe dysplasia. The patient, a 61-year-old woman, showed thickness of the gallbladder wall, detected by ultrasonography and computed temography (CT). Her biliary amylase level in the common bile duct was 103,000 IU/l, and in the gallbladder it was 153,500 IU/l, although endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction. Immunohistochemical staining showed many p53-positive nuclei in the dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse nuclear staining for Ki-67. In the present patient, early diagnosis of occult pancreatobiliary reflux led to early detection of a precancerous lesion of the gallbladder mucosa.

Abdominal Pain↗
PubMed2005

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BACKGROUND: The esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis. METHODS: Chronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats. RESULTS: In the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers. CONCLUSIONS: The localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

Animals↗