Abstract:
BACKGROUND & AIMS:Dkk1 is a secreted antagonist of the Wnt/β-catenin signaling pathway. It is induced by inflammatory cytokines during colitis and exacerbates tissue damage by promoting apoptosis of epithelial cells. However, little is known about the physiologic role of Dkk1 in normal intestinal homeostasis and during wound repair following mucosal injury. We investigated whether inhibition of Dkk1 affects the morphology and function of the adult intestine. METHODS:We used doubleridge mice (Dkk1d/d), which have reduced expression of Dkk1, and an inhibitory Dkk1 antibody to modulate Wnt/β-catenin signaling in the intestine. Intestinal inflammation was induced with dextran sulfate sodium (DSS), followed by a recovery period in which mice were given regular drinking water. Animals were killed before, during, or after DSS administration; epithelial homeostasis and the activity of major signaling pathways were investigated by morphometric analysis, bromo-2'-deoxyuridine incorporation, and immunostaining. RESULTS:Reduced expression of Dkk1 increased proliferation of epithelial cells and lengthened crypts in the large intestine, which was associated with increased transcriptional activity of β-catenin. Crypt extension was particularly striking when Dkk1 was inhibited during acute colitis. Dkk1d/d mice recovered significantly faster from intestinal inflammation but exhibited crypt architectural irregularities and epithelial hyperproliferation compared with wild-type mice. Survival signaling pathways were concurrently up-regulated in Dkk1d/d mice, including the AKT/β-catenin, ERK/Elk-1, and c-Jun pathways. CONCLUSIONS:Dkk1, an antagonist of Wnt/β-catenin signaling, regulates intestinal epithelial homeostasis under physiologic conditions and during inflammation. Depletion of Dkk1 induces a strong proliferative response that promotes wound repair after colitis.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Koch S,Nava P,Addis C,Kim W,Denning TL,Li L,Parkos CA,Nusrat Adoi
10.1053/j.gastro.2011.03.043subject
Has Abstractpub_date
2011-07-01 00:00:00pages
259-68, 268.e1-8issue
1eissn
0016-5085issn
1528-0012pii
S0016-5085(11)00414-8journal_volume
141pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract::The emergence of new glycoprotein structures in colonic mucosa from patients with ulcerative colitis (UC) was assessed through the development of monoclonal antibodies (MAbs). Hybridomas were prepared from mice immunized with mucin glycoproteins purified from UC colonic tissue. Supernatants of 11 fusion products among...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90493-3
更新日期:1988-08-01 00:00:00
abstract::A case of a 41-year-old man with diarrhea, hypoalbuminemia, and cryptogenic cirrhosis with features of portal hypertension is described. Protein-losing enteropathy was confirmed by analysis of whole-gut lavage fluid, and intestinal inflammation and infection were excluded. Distal duodenal biopsy specimens showed evide...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(96)70033-1
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND AND AIMS:The MDR1 gene encodes P-glycoprotein 170, an efflux transporter that is highly expressed in intestinal epithelial cells. The MDR1 exonic single nucleotide polymorphisms (SNPs) C3435T and G2677T have been shown to correlate with activity/expression of P-glycoprotein 170. METHODS:This was a case-cont...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2004.11.019
更新日期:2005-02-01 00:00:00
abstract:BACKGROUND & AIMS:Gastric histology is not well studied in patients with Crohn's disease. The aim of this study was to analyze the histological appearance of gastric mucosa in patients with Crohn's disease. METHODS:In a prospective study, biopsy specimens taken from the antrum and body of 75 patients with known Crohn'...
journal_title:Gastroenterology
pub_type: 评论,杂志文章
doi:10.1053/gast.1997.v112.pm9041230
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND & AIMS:The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). METHODS:Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2012.05.052
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND & AIMS:Noninvasive methods are needed to identify clinically significant portal hypertension (CSPH) and esophageal varices (EVs) in patients with compensated cirrhosis. We looked for markers of the presence of CSPH and EVs in patients with cirrhosis. METHODS:We performed a cross-sectional study that include...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2012.10.001
更新日期:2013-01-01 00:00:00
abstract::To gain further insight on the mosaic expression of specific functional intestinal markers (such as sucrase-isomaltase) in postconfluent Caco-2 cells, a human colon cancer cell line unique in its property to differentiate in vitro into a mature enterocyte-like cell type, a comparative study was undertaken to examine t...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(92)90829-n
更新日期:1992-08-01 00:00:00
abstract::The hypothyroid rat model was used to investigate the effect of dietary-induced hypercholesterolemia on biliary cholesterol content and bile flow. Rats were divided into four dietary groups--diet A: Rat Chow; diet B: Rat Chow plus 0.1% propylthiouracil; diet C: Rat Chow plus 0.1% propylthiouracil, 0.3% taurocholate, 5...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(86)90560-3
更新日期:1986-08-01 00:00:00
abstract::A combination of approaches has begun to elucidate the mechanisms of gastrointestinal development. This review describes progress over the last 20 years in understanding human gastrointestinal development, including data from both human and experimental animal studies that address molecular mechanisms. Rapid progress ...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1016/s0016-5085(99)70193-9
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND & AIMS:During hepatic fibrogenesis, the hepatic extracellular matrix changes to fibrillar collagens types I and III, and cirrhosis is believed to produce an irreversible scar. In this study, we investigated whether gene delivery of human matrix metalloproteinase-1, which degrades collagens types I and type I...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2003.50063
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND & AIMS:Administration of secretin improves noninvasive imaging of the pancreatic duct with magnetic resonance cholangiopancreatography (MRCP). We performed a large prospective study to investigate whether synthetic human secretin (RG1068)-stimulated MRCP detects pancreatic duct abnormalities with higher leve...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2014.05.035
更新日期:2014-09-01 00:00:00
abstract::To study the relationship between gallstone disease (cholelithiasis and cholecystectomy) and cancer, a case-control study was performed in two Swedish hospitals comparing the prevalence of gallstone disease discovered at necropsy in 1422 subjects who died of cancer and 1205 subjects who did not die of cancer. Gallston...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1982-09-01 00:00:00
abstract::The effect of somatostatin 28, a noval intestinal peptide containing somatostatin in its C-terminal portion, was tested on basal exocrine pancreatic secretion on conscious dogs and after stimulation by secretin (1 CU x kg-1 x hr-1), caerulein (37.5 ng x kg-1 x hr-1) or secretin (2 CU x kg-1 x hr-1) caerulein (37.5 ng ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Developmental aspects of the intestinal transport of biotin were examined in suckling (16 day old) and weanling (24 day old) rats using the everted sac technique. The results were compared with those of adult rats previously reported by us using the same intestinal preparation. Transport of biotin was linear for 20 mi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90611-7
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND & AIMS:Caspases are critical mediators of apoptosis and proliferation of peripheral blood T cells (PBT), but their role in lamina propria T cells (LPT), a cell population highly susceptible to apoptosis, has not been explored. METHODS:RA(+), RO(+) PBT, and LPT were activated with CD3, CD2, and CD28 antibodi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2002.32996
更新日期:2002-05-01 00:00:00
abstract::We have studied the effect of short-term high-dose prednisone therapy on aminotransferase levels and hepatitis B virus markers in 6 patients with chronic type B hepatitis. All showed a decrease in amino transferase levels during treatment. This was followed by a transient increase in aminotransferase levels after pred...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Gallbladder stasis has been implicated in gallstone formation. Gallbladder filling and emptying were quantitated by computer-assisted cholescintigraphy in 41 normal subjects versus 26 patients with gallstones. Gallbladder contraction was induced by low-dose (1.2 U/kg . h) cholecystokinin infusion. Gallstone patients e...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(85)90152-0
更新日期:1985-03-01 00:00:00
abstract:BACKGROUND & AIMS:Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 ...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2019.08.008
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND & AIMS:The metabolic and urease responses of Helicobacter pylori to variations in gastric acidity are unknown. The aim of this study was to determine effects of changes of environmental pH on metabolism, urease activity, and survival of H. pylori in an unbuffered environment. METHODS:Bacterial metabolism an...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(98)70142-8
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND & AIMS:Nonalcoholic chronic pancreatitis is usually idiopathic and often associated with cystic fibrosis gene (CFTR) mutations. It is unknown whether pancreatitis risk correlates with having 1 or 2 CFTR mutations, abnormal epithelial ion transport, or mutations of other genes. METHODS:We tested 39 patients ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2001.29673
更新日期:2001-12-01 00:00:00
abstract::Experiments were designed to test the hypothesis that alterations of intestinal motility accompany enteric helminth infections. Motility was measured in rats during the intestinal phase of infection with the nematode Trichinella spiralis by following the transit of radioactive chromium through the gut. Intraduodenal c...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract:BACKGROUND & AIMS:Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended si...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2010.02.053
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND AND AIMS:Autoimmune responses against colonic epithelium may play a role in the development of colonic inflammation associated with ulcerative colitis (UC). In this study, we established and characterized B-cell lines and clones that produced anticolon antibody from inflamed colonic mucosa of UC subjects. M...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2001.25477
更新日期:2001-07-01 00:00:00
abstract::Chlorpromazine (CPZ) is a long recognized cause of jaundice, but the mechanism by which this agent produces icteric liver disease is not well defined. This study examined some effects of CPZ administration on bilirubin metabolism and biliary secretion in the rat. Acute CPZ treatment (25 mg per kg intravenously) produc...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract:BACKGROUND & AIMS:Firmicutes bacteria produce metabolites that maintain the intestinal barrier and mucosal immunity. Firmicutes are reduced in the intestinal microbiota of patients with ulcerative colitis (UC). In a phase 1b trial of patients with UC, we evaluated the safety and efficacy of SER-287, an oral formulation...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2020.07.048
更新日期:2021-01-01 00:00:00
abstract::To determine the fate of exogenous epidermal growth factor (EGF) in regenerating liver, 125I-labeled EGF was injected into rat portal veins at various times after 70% hepatectomy. Epidermal growth factor was taken up by the liver remnant at all time points studied (0, 4, 8, 16, and 36 h), but at 8 h after hepatectomy ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(87)91084-5
更新日期:1987-05-01 00:00:00
abstract::Absorptive cells of the small intestine are highly polarized cells with distinct microvillus membrane (MVM) and basolateral plasma membrane domains. We compared membrane structure in the following preparations of rat small intestine commonly used for in vitro study of MVM function: epithelial sheets, isolated epitheli...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(86)90194-0
更新日期:1986-12-01 00:00:00
abstract:BACKGROUND & AIMS:Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to t...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2010.05.079
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND & AIMS:SMAD4 frequently is lost from colorectal cancers (CRCs), which is associated with the development of metastases and a poor prognosis. SMAD4 loss is believed to alter transforming growth factor β signaling to promote tumor progression. However, SMAD4 is also a central component of the bone morphogeneti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2014.03.052
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND & AIMS:Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. ...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究
doi:10.1053/j.gastro.2015.05.039
更新日期:2015-09-01 00:00:00