Galectin-1 is an inductor of pancreatic stellate cell activation.
Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Here, we show that activation of rat PSCs in vitro is associated with increased expression of galectin-1 (gal-1) and that gal-1 modulates PSC function. Expression of the lectin was stimulated by fetal calf serum and platelet-derived growth factor. PSCs exposed to exogenous gal-1 proliferated at a higher rate and synthesised more collagen than controls. Gal-1-dependent collagen synthesis was blocked by lactose but not by cellobiose, suggesting that gal-1 acts on PSCs through targeting beta-galactoside-containing glycoconjugates. Analysis of gal-1 signalling in PSCs revealed an activation of the extracellular signal-regulated kinases 1 and 2 and enhanced DNA binding of AP-1 transcription factors. Together, our data implicate gal-1 in PSC activation and suggest further studies to analyse the role of endogenous lectins in the development of pancreatic fibrosis in vivo.
Fitzner
Brit
B
Department of Medicine, Division of Gastroenterology, Medical Faculty, University of Rostock, E.-Heydemann-Str. 6, 18057 Rostock, Germany.
Walzel
Hermann
H
Sparmann
Gisela
G
Emmrich
Jörg
J
Liebe
Stefan
S
Jaster
Robert
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D037483:Galectin 1 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D010179:Pancreas / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011392:Proline / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000199:Actins; D000077214:Becaplermin; D003094:Collagen; D016895:Culture Media, Serum-Free; D037483:Galectin 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D009841:Oligonucleotides; D010982:Platelet-Derived Growth Factor; D011392:Proline; D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat