title: TGF-beta-1 up-regulates extra-cellular matrix production in mouse hepatoblasts.
abstract: Fetal liver is the major embryonic hematopoietic organ and is extrinsically colonized by circulating hematopoietic stem cells (HSCs). Integrin beta-1 expression on HSCs is crucial for colonization, suggesting that interaction of Integrin beta-1 with extra-cellular matrix (ECM) factors promotes HSC adherence to fetal liver. However, little is known about how ECM production is regulated in fetal liver. Here we used flow cytometry to sort fetal liver compartments and detected ECM gene and protein expression predominantly in sorted hepatoblasts. mRNA and protein analysis suggested that TGF-beta-1 expressed by hepatoblasts, sinusoid endothelial cells and hematopoietic cells, binds to the TGF-beta receptor type-2 expressed on hepatoblasts to stimulate ECM production. Intra-cardiac injection of TGF-inhibitors into mouse embryos dramatically decreased fetal liver ECM gene expression. Taken together, our observations suggest that hepatoblasts predominantly produce ECM factors under control of TGF-beta-1 in fetal liver.
authors.affiliation: Division of Hematopoietic Stem Cells, Advanced Medical Initiatives, Department of Advanced Medical Initiatives, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. ds-mons@yb3.so-net.ne.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.forename: Kasem
authors.initials: K
authors.lastname: Kulkeaw
authors.forename: Chiyo
authors.initials: C
authors.lastname: Mizuochi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D046149:Embryo Culture Techniques; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D016326:Extracellular Matrix Proteins; D016023:Integrins; D011990:Receptors, Transferrin; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019009:Proto-Oncogene Proteins c-kit