Abstract：
:Pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer, is mediated by activated pancreatic stellate cells (PSC). Connective tissue growth factor (CTGF) has been suggested to play a major role in fibrogenesis by enhancing PSC activation after binding to alpha5beta1 integrin. Here, we have focussed on molecular determinants of CTGF action. Inhibition of CTGF expression in PSC by siRNA was associated with decreased proliferation, while application of exogenous CTGF stimulated both cell growth and collagen synthesis. Real-time PCR studies revealed that CTGF target genes in PSC not only include mediators of matrix remodelling but also the proinflammatory cytokines interleukin (IL)-1beta and IL-6. CTGF stimulated binding of NF-kappaB to the IL-6 promoter, and siRNA targeting the NF-kappaB subunit RelA interfered with CTGF-induced IL-6 expression, implicating the NF-kappaB pathway in the mediation of the CTGF effect. In further studies, we have analyzed regulation of CTGF expression in PSC. Transforming growth factor-beta1, activin A and tumor necrosis factor-alpha enhanced expression of the CTGF gene, while interferon-gamma displayed the opposite effect. The region from -74 to -125 of the CTGF promoter was revealed to be critical for its activity in PSC as well as for the inhibitory effect of interferon-gamma. Taken together, our results indicate a tight control of CTGF expression in PSC at the transcriptional level. CTGF promotes fibrogenesis both directly by enhancing PSC proliferation and matrix protein synthesis, and indirectly through the release of proinflammatory cytokines that may accelerate the process of chronic inflammation.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Karger A,Fitzner B,Brock P,Sparmann G,Emmrich J,Liebe S,Jaster Rdoi
10.1016/j.cellsig.2008.06.016subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1865-72issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00190-3journal_volume
20pub_type
杂志文章abstract：:Activation of the caspase proteases by c-Jun N-terminal kinase 1 (JNK1) has been proposed as a mechanism of apoptotic cell death. Here we report that insulin activates caspase-3 by a pathway requiring phosphatidylinositol 3'-kinase (PI3-kinase). JNK1 assays demonstrated that insulin treatment of myeloma cells induced ...
journal_title：Cellular signalling
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journal_title：Cellular signalling
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journal_title：Cellular signalling
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doi：10.1016/j.cellsig.2009.09.010
更新日期：2010-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2017.01.026
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journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：1995-05-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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更新日期：2005-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(92)90073-h
更新日期：1992-05-01 00:00:00
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journal_title：Cellular signalling
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doi：10.1016/j.cellsig.2016.10.003
更新日期：2017-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.12.008
更新日期：2011-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.109361
更新日期：2019-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(91)90046-w
更新日期：1991-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(02)00014-1
更新日期：2002-08-01 00:00:00
abstract：:The cyclin-dependent kinase inhibitors (CKI) interact with cyclin-cdk complexes to arrest mitogen-stimulated transit through the cell cycle, but we and others have recently shown that these molecules can exert permissive effects on cell cycle transit as well. The p53 protein induces transcription of the p21(Waf1/Cip1)...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00081-4
更新日期：2000-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(96)00119-2
更新日期：1997-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.05.017
更新日期：2008-10-01 00:00:00
abstract：:Ketone bodies β-hydroxybutyrate (BHB) and acetoacetate are important metabolic substrates for energy production during prolonged fasting. However, BHB also has signaling functions. Through several metabolic pathways or processes, BHB modulates nutrient utilization and energy expenditure. These findings suggest that BH...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2016.04.005
更新日期：2016-08-01 00:00:00
abstract：:Nuclear factor of activated T cells (NFAT) plays a prominent role in gene transcription during the immune response. Growing evidence demonstrates the implication of inducible phosphorylation of the transactivation domain (TAD) of NFAT in transcriptional activation of genes. We have analyzed the regulation of NFATc2 ac...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2007.02.010
更新日期：2007-08-01 00:00:00
abstract：:Both sphingosine-1-phosphate receptor-2 (S1PR2) and cytosolic phospholipase A2 (cPLA2) are implicated in the disruption of cerebrovascular integrity in experimental stroke. However, the role of S1PR2 in induction of cPLA2 phosphorylation during cerebral ischemia-induced endothelial dysfunction remains unknown. This st...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.09.019
更新日期：2019-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2009.10.003
更新日期：2010-03-01 00:00:00
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journal_title：Cellular signalling
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更新日期：2018-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.09.011
更新日期：2013-12-01 00:00:00
abstract：:Growing evidence shows that chronic inflammation drives the progression of colorectal cancer (CRC). Cyclooxygenase-2 (COX-2) is one of the most important inflammatory genes involved in solid tumor metastasis. Epidermal growth factor receptor (EGFR) also plays a key role in cancer cell development. We compared the expr...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.08.017
更新日期：2012-01-01 00:00:00
abstract：:Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(02)00120-1
更新日期：2003-05-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.09.007
更新日期：2011-01-01 00:00:00
abstract：:Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2003.09.005
更新日期：2004-05-01 00:00:00
abstract：:Recent studies have shown DAPk as a molecular modulator induced by the second messenger, responsible for controlling cell destiny decisions, but the detailed mechanism mediating the role of DAPk1 during cell death is still not fully understood. In this present report, we attempted to characterize the effects of TNF-α ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.03.010
更新日期：2012-07-01 00:00:00
abstract：:Exponentially growing V79 Chinese hamster lung fibroblasts irradiated with 7 Gy X-rays undergo cell cycle arrest in the S and G2 phases. These arrests are released, probably on completion of DNA repair. A premature release occurs after treatment of irradiated cells with caffeine. This release is accompanied by increas...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(94)90008-6
更新日期：1994-07-01 00:00:00
abstract：:A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidenc...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.06.015
更新日期：2018-10-01 00:00:00
abstract：:Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PC...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.06.002
更新日期：2016-09-01 00:00:00
