Nodal and lefty signaling regulates the growth of pancreatic cells.
Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co-receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and regeneration. We found that both Nodal and Lefty are expressed in the pancreas during embryogenesis and islet regeneration. In vitro studies demonstrated that Nodal inhibits, whereas Lefty enhances, the proliferation of a pancreatic cell line. In addition, we showed that Lefty-1 activates MAPK and Akt phosphorylation in these cells. In vivo blockade of endogenous Lefty using neutralizing Lefty-1 monoclonal antibody results in a significantly decreased proliferation of duct epithelial cells during islet regeneration. This is the first study to decipher the expression and function of Nodal and Lefty in pancreatic growth. Importantly, our results highlight a novel function of Nodal-Lefty signaling in the regulation of expansion of pancreatic cells.
Zhang
You-Qing
YQ
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Sterling
Lori
L
Stotland
Aleksandr
A
Hua
Hong
H
Kritzik
Marcie
M
Sarvetnick
Nora
N
D028341:Activins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology; D055458:Left-Right Determination Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D055457:Nodal Protein; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D055458:Left-Right Determination Factors; D055457:Nodal Protein; C526008:Nodal protein, mouse; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases