Pancreatic Extracellular Matrix Alterations in Chronic Pancreatitis

Kennedy, Robin H.; Bockman, Dale E.; Uscanga, Luis; Choux, R; Grimaud, Jean‐Alexis; Sarles, H

doi:10.1097/00006676-198701000-00010

Cited by 85 publications

(42 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3] Further, various amounts of inflammatory cell infiltrates, acinar cell degeneration, and the dedifferentiation of acinar cells into ductlike tubular complexes, as well as to a minor extent ductal cell proliferation, are typical histologic characteristics of CP. [3][4][5] The destruction of the exocrine pancreatic parenchyma leads to various degrees of maldigestion. The other dominant clinical symptom in CP is recurrent abdominal pain, which occurs in approximately 80% to 90% of the patients.…”

Section: Resultsmentioning

confidence: 99%

Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis

Frieß¹,

Zhu²,

Mola³

et al. 1999

Annals of Surgery

160

100

View full text Add to dashboard Cite

ObjectiveTo study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). Summary Background DataChronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. MethodsNerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. ResultsBy Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p Ͻ 0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p Ͻ 0.05) between NGF mRNA levels and pancreatic fibrosis (r ϭ 0.64) and acinar cell damage (r ϭ 0.74) and between TrkA mRNA and pain intensity (r ϭ 0.84).

show abstract

Section: Resultsmentioning

confidence: 99%

Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis

Frieß¹,

Zhu²,

Mola³

et al. 1999

Annals of Surgery

160

100

View full text Add to dashboard Cite

show abstract

“…Extracellular matrix (ECM) components are distributed in both healthy and diseased pancreas, and there is an increased deposition of disorganized ECM components in chronic pancreatitis [2] . However, the mechanism of the fibrotic process is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Effect of emodin on pancreatic fibrosis in rats

Wang

Gao²,

Yu³

et al. 2007

WJG

View full text Add to dashboard Cite

AIM:To establish the rats model of chronic fibrosing pancreatitis and to prove the anti-fibrotic effect of emodin in chronic pancreatitis with fibrosis. METHODS:Fifty rats were randomly divided into five groups, 10 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was infused into the pancreatic duct to induce chronic pancreatitis in rats (except for normal group). Emodin-treated rats were fed with different doses of emodin (20, 40 and 80 mg/kg body weight) for 28 d, while normal group and control group received 0.9% sodium chloride solution. Serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. Histopathological alterations were studied by optical microscopy. Expression of collagen was also examined while transforming growth factorbeta-1 (TGF-β1) was localized by immunochemistry. RESULTS:In emodin-treated rats, the serum levels of HA and LN were decreased significantly (HA, 62.2 ± 19.3 µg/L vs 112.7 ± 26.5 µg/L, P < 0.05; LN 44.3 ± 10.4 µg/L vs 86.2 ± 16.5 µg/L, P < 0.05); the degree of fibrosis was ameliorated observably; the expression of collagen in pancreatic tissue was reduced especially in high-dose emodin-treated group (36% ± 5% vs 42% ± 6%, P < 0.05); with the increased doses of emodin, the expression of TGF-β1 was declined, compared with those in control group. CONCLUSION:Emodin has an anti-fibrotic effect on pancreatic fibrosis in rats. Because of its anti-fibrotic effect, it could be a potential herb for the treatment of chronic pancreatitis.

show abstract

“…[1][2][3][4] In liver cirrhosis, hepatic stellate cells (HSC) have been identified to be the main source of extracellular matrix (ECM) deposition. [5][6][7] Similarly, the recently identified pancreatic stellate cells (PSC) have been implicated in the development of fibrotic tissue in the pancreas in chronic pancreatitis and in pancreatic cancer.…”

mentioning

confidence: 99%

Immortalization of pancreatic stellate cells as an in vitro model of pancreatic fibrosis: deactivation is induced by matrigel and N-acetylcysteine

Jesnowski

Fürst

Ringel

et al. 2005

Laboratory Investigation

132

134

View full text Add to dashboard Cite

Tissue fibrosis is one of the characteristics of chronic pancreatitis and pancreatic adenocarcinoma. Activated pancreatic stellate cells (PSC) play a central role in this process. However, analysis of the molecular mechanisms leading to PSC activation is hampered by the lack of an established human PSC line. To overcome this problem, we immortalized and characterized primary human PSC. The cells were isolated by the outgrowth method and were immortalized by transfection with SV40 large T antigen and human telomerase (hTERT). Primary human PSC served as controls. An immortalized line, RLT-PSC, was analyzed for the expression of stellate cell markers. Moreover, the effects of transforming growth factor b 1(TGFb1) or platelet-derived growth factor stimulation and of cultivation on basement membrane components or N-acetylcysteine (NAC) treatment on gene and protein expression and proliferation were analyzed. Immortal RLT-PSC cells retained the phenotype of activated PSC proven by the expression of a-smooth muscle actin (aSMA), vimentin, desmin and glial fibrillary acidic protein (GFAP). TGFb1 treatment upregulated the expression of aSMA, collagen type I (Col I), fibronectin and TGFb1. Incubation of RLT-PSC cells and primary human activated PSC on Matrigel plus NAC treatment resulted in a deactivated phenotype as evidenced by a decrease of aSMA, connective tissue growth factor and Col I expression and by a decreased proliferation of the cells. Moreover, this treatment restored the ability of the cells to store vitamin A in cytoplasmic vesicles. In conclusion, we have established an immortal pancreatic stellate cell line, without changing the characteristic phenotype. Importantly, we were able to demonstrate that besides soluble factors, the matrix surrounding PSC plays a pivotal role in the maintenance of the activation process of PSC. Cultivation of activated PSC on a reconstituted basement membrane plus treatment with NAC was able to deactivate the cells, thus pointing to the possibility of an antifibrosis therapy in chronic pancreatitis.

show abstract

Pancreatic Extracellular Matrix Alterations in Chronic Pancreatitis

Cited by 85 publications

References 0 publications

Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis

Nerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis

Effect of emodin on pancreatic fibrosis in rats

Immortalization of pancreatic stellate cells as an in vitro model of pancreatic fibrosis: deactivation is induced by matrigel and N-acetylcysteine

Contact Info

Product

Resources

About