Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes.

Abstract:

BACKGROUND AND OBJECTIVE:Fibrosis associated with chronic pancreatitis is an irreversible lesion that can disrupt pancreatic exocrine and endocrine function. Currently, there are no approved treatments for this disease. We previously showed that siRNA against collagen-specific chaperone protein gp46, encapsulated in vitamin A-coupled liposomes (VA-lip-siRNAgp46), resolved fibrosis in a model of liver cirrhosis. This treatment was investigated for pancreatic fibrosis induced by dibutyltin dichloride (DBTC) and cerulein in rats. METHODS:Specific uptake of VA-lip-siRNAgp46, conjugated with 6'-carboxyfluorescein (FAM) by activated pancreatic stellate cells (aPSCs), was analysed by fluorescence activated cell sorting (FACS). Intracellular distribution of VA-lip-siRNAgp46-FAM was examined by fluorescent microscopy. Suppression of gp46 expression by VA-lip-siRNAgp46 was assessed by immunoblotting. Collagen synthesis in aPSCs was assayed by dye-binding. Specific delivery of VA-lip-siRNAgp46 to aPSCs in DBTC rats was verified following intravenous VA-lip-siRNA-FAM and (3)H-VA-lip-siRNAgp46. The effect of VA-lip-siRNA on pancreatic histology in DBTC- and cerulein-treated rats was determined by Azan-Mallory staining and hydroxyproline content. RESULTS:FACS analysis revealed specific uptake of VA-lip-siRNAgp46-FAM through the retinol binding protein receptor by aPSCs in vitro. Immunoblotting and collagen assay verified knockdown of gp46 and suppression of collagen secretion, respectively, by aPSCs after transduction of VA-lip-siRNAgp46. Specific delivery of VA-lip-siRNAgp46 to aPSCs in fibrotic areas in DBTC rats was confirmed by fluorescence and radioactivity 24 h after the final injection. 10 systemic VA-lip-siRNAgp46 treatments resolved pancreatic fibrosis, and suppressed tissue hydroxyproline levels in DBTC- and cerulein-treated rats. CONCLUSION:These data suggest the therapeutic potential of the present approach for reversing pancreatic fibrosis.

journal_name

Gut

journal_title

Gut

authors

Ishiwatari H,Sato Y,Murase K,Yoneda A,Fujita R,Nishita H,Birukawa NK,Hayashi T,Sato T,Miyanishi K,Takimoto R,Kobune M,Ota S,Kimura Y,Hirata K,Kato J,Niitsu Y

doi

10.1136/gutjnl-2011-301746

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

1328-39

issue

9

eissn

0017-5749

issn

1468-3288

pii

gutjnl-2011-301746

journal_volume

62

pub_type

杂志文章

相关文献

GUT文献大全
  • Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: a Dutch-Scandinavian collaborative study including 659 patients.

    abstract:BACKGROUND AND AIMS:The choice of colorectal surgery in patients with familial adenomatous polyposis lies between the morbidity of proctocolectomy and ileum-pouch-anal anastomosis (IPAA) and the mortality from rectal cancer after total colectomy and ileorectal anastomosis (IRA). The aims of the present study were: (1) ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.49.2.231

    authors: Vasen HF,van Duijvendijk P,Buskens E,Bülow C,Björk J,Järvinen HJ,Bülow S

    更新日期:2001-08-01 00:00:00

  • Developmental aspects of human hepatic drug glucuronidation in young children and adults.

    abstract:BACKGROUND AND AIMS:The liver represents one of the major sites of human glucuronidation. Many therapeutic drugs are substrates for UDP-glucuronosyltransferases (UGT) leading to the formation of usually inactive glucuronides. Hepatic glucuronidation undergoes significant changes during fetal and neonatal development re...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.50.2.259

    authors: Strassburg CP,Strassburg A,Kneip S,Barut A,Tukey RH,Rodeck B,Manns MP

    更新日期:2002-02-01 00:00:00

  • Response to autoimmune enteropathy to cyclosporin A therapy.

    abstract::Small bowel enteropathies that are associated with an autoimmune process are often resistant to treatment. Two children with autoimmune enteropathy were treated with cyclosporin A for eight months. Both improved, as assessed by growth, small intestinal mucosal morphology, and carbohydrate absorption. Cyclosporin A is ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.32.11.1421

    authors: Sanderson IR,Phillips AD,Spencer J,Walker-Smith JA

    更新日期:1991-11-01 00:00:00

  • Relation between gastric cancer and previous peptic ulcer disease.

    abstract:BACKGROUND:It is presently not well understood to what extent peptic ulcer and gastric cancer represent related diseases. AIMS:The objective of this study was to assess past occurrence of gastric and duodenal ulcers in patients with cancer of the gastric cardia or other parts of the stomach. METHODS:The association b...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.40.2.247

    authors: Molloy RM,Sonnenberg A

    更新日期:1997-02-01 00:00:00

  • Compliance of adolescents with coeliac disease with a gluten free diet.

    abstract::A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtain...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.32.8.881

    authors: Mayer M,Greco L,Troncone R,Auricchio S,Marsh MN

    更新日期:1991-08-01 00:00:00

  • Potential difference across the normal and the abnormal gastric mucosa in man.

    abstract::The mucosal potential difference in the body of the stomach was measured in 18 patients with gastric ulcers, five with gastritis, and three with pernicious anaemia. The results were compared with those of 12 normal volunteers. Significantly lower than normal levels were found in the groups of patients with gastric ulc...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.17.12.993

    authors: Hossenbocus A,Fitzpatrick P,Colin-Jones DG

    更新日期:1976-12-01 00:00:00

  • Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease.

    abstract:BACKGROUND:There is considerable evidence indicating that the severity of hepatic damage in individuals with cholestatic liver disease is causally associated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid pe...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.47.5.710

    authors: Ljubuncic P,Tanne Z,Bomzon A

    更新日期:2000-11-01 00:00:00

  • The effect of anticholinergic drugs on the mucus content of gastric juice.

    abstract::Increasing suppression of gastric secretion by anticholinergic drugs is accompanied by a rising mucus concentration; the actual output of mucus shows little change despite a marked reduction in the secretory volume. The problems involved in the estimation of mucus secretion and the importance of the above findings in ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.3.2.177

    authors: PIPER DW,STIEL MC,FENTON B

    更新日期:1962-06-01 00:00:00

  • Acid, motility, and ulcers: a comparison of cisapride with placebo in the prevention of duodenal ulcer relapse.

    abstract::In a single centre double blind study of 66 patients, the value of cisapride (10 mg twice daily) was compared with placebo in the prevention of duodenal ulcer relapse. Patients who remained ulcer free attended for clinical review every two months and had a mandatory endoscopy at 0, 4, 8, and 12 months or if symptoms s...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.34.8.1042

    authors: Kerrigan DD,Taylor ME,Read NW,Johnson AG

    更新日期:1993-08-01 00:00:00

  • Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression.

    abstract:OBJECTIVE:Endoscopic surveillance for Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage an...

    journal_title:Gut

    pub_type: 杂志文章,多中心研究

    doi:10.1136/gutjnl-2014-308802

    authors: Kastelein F,van Olphen SH,Steyerberg EW,Spaander MC,Bruno MJ,ProBar-Study Group.

    更新日期:2016-04-01 00:00:00

  • Effects of supplemental oxygen on cardiac rhythm during upper gastrointestinal endoscopy: a randomised controlled double blind trial.

    abstract::To investigate the effects of supplemental oxygen on cardiac rhythm during gastroscopy, 103 patients aged over 60 were randomised to receive either supplemental oxygen or air at 2 litres/minute during the procedure. Pulse rate, blood pressure, oxygen saturation, and a Holter cardiac trace were monitored before, during...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.34.11.1492

    authors: Bowling TE,Hadjiminas CL,Polson RJ,Baron JH,Foale RA

    更新日期:1993-11-01 00:00:00

  • Volvulus of the small intestine in adults.

    abstract::Five cases of volvulus of varying lengths of the small intestine are described. The incidence and the aetiology of the condition are briefly discussed. Shock as a feature of extensive volvulus is stressed, and its cause in these cases is related to the previous animal experimental work of others. The other clinical fe...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.1.1.76

    authors: TALBOT CH

    更新日期:1960-03-01 00:00:00

  • Behaviour of acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids over six months from eradication of helicobacter pylori in duodenal ulcer patients. A controlled study.

    abstract::The behaviour of basal and stimulated acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months afte...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.37.2.210

    authors: Parente F,Maconi G,Sangaletti O,Minguzzi M,Vago L,Bianchi Porro G

    更新日期:1995-08-01 00:00:00

  • An interim report on the production of colonic diverticula in the rabbit.

    abstract::Six New Zealand white rabbits were given gas induction anaesthetics and maintained on glucochloralose (Merck) 60 mg/kg given intravenously. Intracolonic pressures were measured after a standard dose of prostigmine, 0.05 mg/kg, using fluid-filled, open-tipped, narrow-bore polythene tubes. Then the rabbits were put on a...

    journal_title:Gut

    pub_type: 杂志文章

    doi:

    authors: Hodgson WJ

    更新日期:1972-10-01 00:00:00

  • Metabolism of 125I-labelled trypsin in man: evidence of recirculation.

    abstract::125I-labelled human trypsin metabolism has been investigated in man. Three subjects received 125I-trypsin and 131I-albumin intravenously. Against a background secretin infusion (1 U/kg/h), trypsin decayed biexponentially from the serum with half-lives of 17.5, 21, and 24 minutes for the rapid disappearance phase and 5...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.21.7.580

    authors: Lake-Bakaar G,Rubio CE,McKavanagh S,Potter BJ,Summerfield JA

    更新日期:1980-07-01 00:00:00

  • Intestinal permeability to polyethyleneglycol 600 in Crohn's disease. Peroperative determination in a defined segment of the small intestine.

    abstract::Ileal permeability to different sized polyethyleneglycols (590-942 dalton PEG) was investigated peroperatively in 11 patients with Crohn's disease and seven with colonic carcinoma. A 15 cm ileal segment was converted into a tied loop, in which the PEG's were deposited. Absorption from the ileal segment was then measur...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.29.2.196

    authors: Olaison G,Leandersson P,Sjödahl R,Tagesson C

    更新日期:1988-02-01 00:00:00

  • Cellular response to alpha-gliadin in untreated coeliac disease.

    abstract::An improved technique for the detection of alpha-gliadin sensitised mononuclear cells in the peripheral blood of untreated coeliac patients is described. This method is a modification of the direct LMIF assay, and involves exposure of lymphocytes to alpha-gliadin and the assay of the resultant lymphokine produced usin...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.23.1.83

    authors: O'Farrelly C,Feighery C,Greally JF,Weir DG

    更新日期:1982-01-01 00:00:00

  • Hepatitis C virus markers in patients with acute post-transfusion hepatitis treated with interferon alfa-2b.

    abstract::This trial was undertaken to establish the long term biochemical and serological outcome of patients with acute post-transfusion hepatitis C virus infection after treatment with interferon alfa-2b. After 12 months, 12 patients (eight treated, four controls) had self limited disease and 16 patients (seven treated, nine...

    journal_title:Gut

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1136/gut.34.2_suppl.s62

    authors: Genesca J,Esteban JI,Quer J,Viladomiu LL,Gonzalez A,Esteban R,Guardia J

    更新日期:1993-01-01 00:00:00

  • IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease.

    abstract::Serum samples from 26 monozygotic twin pairs concordant or discordant with regard to inflammatory bowel disease, and rectal biopsies from 42 twins of the same subject group, were examined for IgG subclasses. They were all compared with normal controls. Almost all affected twins were in clinical remission. Paired immun...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.33.10.1358

    authors: Helgeland L,Tysk C,Järnerot G,Kett K,Lindberg E,Danielsson D,Andersen SN,Brandtzaeg P

    更新日期:1992-10-01 00:00:00

  • Concurrent PEDF deficiency and Kras mutation induce invasive pancreatic cancer and adipose-rich stroma in mice.

    abstract:BACKGROUND AND AIMS:Pigment epithelium-derived factor (PEDF), a non-inhibitory SERPIN with potent antiangiogenic activity, has been recently implicated in metabolism and adipogenesis, both of which are known to influence pancreatic cancer progression. Increased pancreatic fat in human pancreatic tumour correlates with ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gutjnl-2011-300821

    authors: Grippo PJ,Fitchev PS,Bentrem DJ,Melstrom LG,Dangi-Garimella S,Krantz SB,Heiferman MJ,Chung C,Adrian K,Cornwell ML,Flesche JB,Rao SM,Talamonti MS,Munshi HG,Crawford SE

    更新日期:2012-10-01 00:00:00

  • Incorporation of intermediary products of 5-FU anabolism into colorectal cancer.

    abstract::In 18 patients intermediary anabolic metabolites of 5-FU were measured in normal colonic mucosa and colorectal cancer tissue of intravenous bolus injection or continuous infusion. Higher total concentrations of 5-FU products were found in the cancers when compared with normal colonic tissue. There appeared to be no ev...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.27.2.176

    authors: Giles GR,Woodhouse L,Finan PJ,Chisholm EM

    更新日期:1986-02-01 00:00:00

  • Small intestinal structure and passive permeability in systemic sclerosis.

    abstract::Seventeen patients with proven systemic sclerosis had a peroral jejunal biopsy performed. Four biopsies were regarded as showing abnormalities, which were mostly confined to the deeper structures, although in two there was a minimal degree of villous atrophy without epithelial cell changes. Passive intestinal permeabi...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.21.4.293

    authors: Cobden I,Rothwell J,Axon AT,Dixon MF,Lintott DJ,Rowell NR

    更新日期:1980-04-01 00:00:00

  • Role of alkaline phosphatase in colitis in man and rats.

    abstract:BACKGROUND AND AIMS:Crohn's disease (CD) and ulcerative colitis (UC) are chronic multifactorial inflammatory bowel diseases (IBDs) with unknown aetiology, but a deregulated mucosal immune response to gut-derived bacterial antigens is thought to be involved. Toll-like receptor ligands, especially lipopolysaccharide (LPS...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2007.128868

    authors: Tuin A,Poelstra K,de Jager-Krikken A,Bok L,Raaben W,Velders MP,Dijkstra G

    更新日期:2009-03-01 00:00:00

  • Hepatitis B virus protein preS2 potentially promotes HCC development via its transcriptional activation of hTERT.

    abstract:BACKGROUNDS AND AIMS:Telomerase is significantly reactivated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Our previous studies showed that the transactivation unit of HBV surface (S) gene, preS2, could upregulate human telomerase reverse transcriptase (hTERT) expression and telomerase activity ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.2008.174029

    authors: Luan F,Liu H,Gao L,Liu J,Sun Z,Ju Y,Hou N,Guo C,Liang X,Zhang L,Sun W,Ma C

    更新日期:2009-11-01 00:00:00

  • Pancreatogram in cholestasis.

    abstract::Endoscopic retrograde pancreatograms have been examined in patients presenting with cholestasis caused by either primary sclerosing cholangitis (13 subjects), or high cholangiocarcinomata (15 subjects), and in normal individuals (13 subjects). Pancreatograms were reported by two independent observers who had no knowle...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.25.4.424

    authors: Palmer KR,Cotton PB,Chapman M

    更新日期:1984-04-01 00:00:00

  • Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer.

    abstract:INTRODUCTION:In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. MET...

    journal_title:Gut

    pub_type: 杂志文章,多中心研究

    doi:10.1136/gutjnl-2014-308762

    authors: Tol JA,van Hooft JE,Timmer R,Kubben FJ,van der Harst E,de Hingh IH,Vleggaar FP,Molenaar IQ,Keulemans YC,Boerma D,Bruno MJ,Schoon EJ,van der Gaag NA,Besselink MG,Fockens P,van Gulik TM,Rauws EA,Busch OR,Gouma DJ

    更新日期:2016-12-01 00:00:00

  • Ten year follow up of ulcerative colitis patients with and without low grade dysplasia.

    abstract:BACKGROUND AND AIMS:Low grade dysplasia (LGD) is believed to predispose to colorectal cancer (CRC), and proctocolectomy has been advocated when this is identified. Between 1978 and 1990, 160 patients with longstanding extensive ulcerative colitis (UC) were recruited for annual colonoscopic surveillance and 40 developed...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.52.8.1127

    authors: Lim CH,Dixon MF,Vail A,Forman D,Lynch DA,Axon AT

    更新日期:2003-08-01 00:00:00

  • Biliary lipid output during three meals and an overnight fast. II. Effect of chenodeoxycholic acid treatment in gallstone subjects.

    abstract::Oral treatment with chenodeoxycholic acid causes dissolution of cholesterol gallstones in man. In order to determine the mechanism of this effect, we have measured 24-hour biliary lipid output, lipid composition of fasting gallbladder bile, and bile acid pool sizes before and during such treatment in six patients with...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.16.1.12

    authors: Northfield TC,LaRusso NF,Hofmann AF,Thistle JL

    更新日期:1975-01-01 00:00:00

  • Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy.

    abstract::Helicobacter pylori causes chronic (type B) gastritis. The 'intestinal' form of gastric cancer arises against a background of chronic gastritis, and prospective epidemiological studies have shown that H pylori is a major risk factor for this. An increase in mucosal cell proliferation increases the likelihood of a neop...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.36.3.346

    authors: Lynch DA,Mapstone NP,Clarke AM,Sobala GM,Jackson P,Morrison L,Dixon MF,Quirke P,Axon AT

    更新日期:1995-03-01 00:00:00

  • Immunological studies in patients with Crohn's disease.

    abstract::An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and ...

    journal_title:Gut

    pub_type: 杂志文章

    doi:10.1136/gut.17.2.100

    authors: MacPherson BR,Albertini RJ,Beeken WL

    更新日期:1976-02-01 00:00:00