RGD Reference Report - Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells. - Rat Genome Database

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Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells.

Authors: Aoki, H  Ohnishi, H  Hama, K  Ishijima, T  Satoh, Y  Hanatsuka, K  Ohashi, A  Wada, S  Miyata, T  Kita, H  Yamamoto, H  Osawa, H  Sato, K  Tamada, K  Yasuda, H  Mashima, H  Sugano, K 
Citation: Aoki H, etal., Am J Physiol Cell Physiol. 2006 Apr;290(4):C1100-8. Epub 2005 Dec 21.
RGD ID: 2300404
Pubmed: PMID:16371439   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpcell.00465.2005   (Journal Full-text)

Pancreatic stellate cells (PSCs) are activated during pancreatitis and promote pancreatic fibrosis by producing and secreting ECMs such as collagen and fibronectin. IL-1beta has been assumed to participate in pancreatic fibrosis by activating PSCs. Activated PSCs secrete various cytokines that regulate PSC function. In this study, we have examined IL-1beta secretion from culture-activated PSCs as well as its regulatory mechanism. RT-PCR and ELISA have demonstrated that PSCs express IL-1beta mRNA and secrete IL-1beta peptide. Inhibition of TGF-beta(1) activity secreted from PSCs by TGF-beta(1)-neutralizing antibody attenuated IL-1beta secretion from PSCs. Exogenous TGF-beta(1) increased IL-1beta expression and secretion by PSCs in a dose-dependent manner. Adenovirus-mediated expression of dominant-negative (dn)Smad2/3 expression reduced both basal and TGF-beta(1)-stimulated IL-1beta expression and secretion by PSCs. Coexpression of Smad3 with dnSmad2/3 restored IL-1beta expression and secretion by PSCs, which were attenuated by dnSmad2/3 expression. In contrast, coexpression of Smad2 with dnSmad2/3 did not alter them. Furthermore, inhibition of IL-1beta activity secreted from PSCs by IL-1beta-neutralizing antibody attenuated TGF-beta(1) secretion from PSCs. Exogenous IL-1beta enhanced TGF-beta(1) expression and secretion by PSCs. IL-1beta activated ERK, and PD-98059, a MEK1 inhibitor, blocked IL-1beta enhancement of TGF-beta(1) expression and secretion by PSCs. We propose that an autocrine loop exists between TGF-beta(1) and IL-1beta in activated PSCs through Smad3- and ERK-dependent pathways.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of interleukin-1 beta production  IMP 2300404TGFbeta-1 dependent and in pancreatic stellate cellsRGD 
transforming growth factor beta receptor signaling pathway  IMP 2300404TGFbeta-1 dependent and in pancreatic stellate cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad3  (SMAD family member 3)


Additional Information