No abstract available.
Activins* ; Regeneration*

OBJECTIVETo examine the expression of activin A (ACT A) and transforming growth factor-beta 1 (TGF-beta 1) during mandibular lengthening and elucidate the difference between the role of ACT A and TGF-beta 1 during mandibular distraction osteogenesis.

METHODSkeletally mature white new zealand rabbits were established right mandibular distraction osteogenesis model. The regenerating tissue of animals' lengthened mandibes were harvested at different time points to have immunohistochemistric research of ACT A, TGF-beta 1 protein and analysis ACT A, TGF-beta 1 mRNA by using RT-PCR semiquantitative mean.

RESULTSAT the end of latency period day, positive stain of ACT A were found in the osteoblasts while positive stain of TGF-beta 1 was found in mesenchymal cells. At the end of distraction phase, fibrosis tissue had no stain of ACT A, but had strong stain of TGF-beta 1. At the period of fixation days of 20 days, both cytoplasm of osteoblasts and extracellular matrix in primary mineralization front were strongly stained of ACT A. The osteoblasts, osteoid and osteocytes in peripheral new bone zone were moderately stained of ACT A. TGF-beta 1 had strongly positive stained in fibrosis zone and weekly positive stained in primary mineralization front and peripheral new bone zone. There were also broad activin A stains in cytoplasm of osteoblasts, osteoid and cytoplasm of ACT A, TGF-beta 1 in osteocytes after distraction for 30 days. Activin A mRNA began to express at the end of latency period. Expression for activin A mRNA increased gradually along with the beginning of distraction and at the peak in distraction of 10 days and 20 days, while TGF beta 1 mRNA increased at the peak at the end of latency period.

CONCLUSIONACT A and TGF beta 1 have different role during rabbit mandibular distraction osteogenesis.

Activins ; analysis ; physiology ; Animals ; Female ; Immunohistochemistry ; Inhibin-beta Subunits ; analysis ; physiology ; Mandible ; surgery ; Osteogenesis, Distraction ; Rabbits ; Transforming Growth Factor beta ; analysis ; physiology ; Transforming Growth Factor beta1

No abstract available.
Activins* ; Humans ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis*

No abstract available.
Activins* ; Humans ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis*

PURPOSE: The most important consideration for therapy using MSCs is the differentiation of the target organ's cell type. For in-vitro hepatogenic differentiation of MSCs, the main focus is efficient induction of the MSCs into the endoderm stage. Activin A, which is a signaling molecule that is similar to Nodal, promotes the induction of definitive endoderm from both ESs and MSCs. The protocols for induction into definitive endoderm have shown different efficiency and reproducibility depending on the researchers or the sources of the MSCs. Thus, a study on the various conditions of Activin A is needed to efficiently differentiate MSCs into the definitive endoderm lineage of MSCs. METHODS: MSCs were isolated from human adipose tissues and these were cultured in MCM (MSCs Culture Medium) on a human fibronectin coated plate. At 70~80% confluence, the MSCs were harvested and cultured in MCM supplemented with Activin A, at a 50 ng/mL concentration, and FGF4. The expression of the genes related with MSCs or primitive endoderm were analyzed by RT-PCR. The changes of cell morphology for differentiation were also observed by a light microscope & a SEM. RESULTS: The expression of genes related with primitive foregut endoderm was seen in the groups that were treated with a higher concentration of Activin A. The morphology of the cells that differentiated into definitive endoderm were not different from those of the undifferentiated MSCs. The expression of genes related with functional primitive hepatocytes was seen in the early phase during hepatic differentiation. The cell morphology was changed to a similar cuboidal form in a time-dependent manner. CONCLUSION: Activin A promotes a more rapid induction of definitive endoderm. It also makes an efficient condition for the differentiation into primitive foregut endoderm at a higher concentration.
Activins ; Endoderm ; Fibronectins ; Hepatocytes ; Humans ; Light

PURPOSE: The most important consideration for therapy using MSCs is the differentiation of the target organ's cell type. For in-vitro hepatogenic differentiation of MSCs, the main focus is efficient induction of the MSCs into the endoderm stage. Activin A, which is a signaling molecule that is similar to Nodal, promotes the induction of definitive endoderm from both ESs and MSCs. The protocols for induction into definitive endoderm have shown different efficiency and reproducibility depending on the researchers or the sources of the MSCs. Thus, a study on the various conditions of Activin A is needed to efficiently differentiate MSCs into the definitive endoderm lineage of MSCs. METHODS: MSCs were isolated from human adipose tissues and these were cultured in MCM (MSCs Culture Medium) on a human fibronectin coated plate. At 70~80% confluence, the MSCs were harvested and cultured in MCM supplemented with Activin A, at a 50 ng/mL concentration, and FGF4. The expression of the genes related with MSCs or primitive endoderm were analyzed by RT-PCR. The changes of cell morphology for differentiation were also observed by a light microscope & a SEM. RESULTS: The expression of genes related with primitive foregut endoderm was seen in the groups that were treated with a higher concentration of Activin A. The morphology of the cells that differentiated into definitive endoderm were not different from those of the undifferentiated MSCs. The expression of genes related with functional primitive hepatocytes was seen in the early phase during hepatic differentiation. The cell morphology was changed to a similar cuboidal form in a time-dependent manner. CONCLUSION: Activin A promotes a more rapid induction of definitive endoderm. It also makes an efficient condition for the differentiation into primitive foregut endoderm at a higher concentration.
Activins ; Endoderm ; Fibronectins ; Hepatocytes ; Humans ; Light

Pregnancy ; Female ; Humans ; Activins ; Hypertension ; Biomarkers

OBJECTIVETo examine the expression changes of activin beta A, beta C, beta E and follistatin mRNA in the development of rat hepatic fibrosis induced by carbon tetrachloride (CCl(4)).

METHODSHepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. After carbon tetrachloride injection of 1, 2, 3, 4, 5, 6, and 7 weeks, the 6-12 rats were killed every time. The kinetics of activin beta A, beta C, beta E and follistatin mRNA expression were assessed by the semi-quantity RT-PCR.

RESULTSActivin beta A, beta C, beta E and follistatin mRNA could be detected in normal rat livers. After CCl(4) injection for 2 or 3 weeks, beta A mRNA was transiently decreased and became undetectable, then increased gradually. After CCl injection for 6 and 7 weeks, beta A mRNA level was significantly higher than controls (P<0.01). beta C mRNA could be detected after CCl(4) injection for 1 to 4 weeks and was significantly increased after 5 weeks over controls (P<0.05). beta E mRNA could not be detected after CCl(4) injection for 1 to 5 weeks, but significantly increased after CCl(4) injection for 6 or 7 weeks compared with controls (P<0.01). Except for normal rat liver, no follistatin mRNA was detected in rats after CCl(4) injection.

CONCLUSIONSActivins and follistatin have different expression changes in the development of hepatic fibrosis and the imbalance of activins and follistatin expression may involve in the formation of hepatic fibrosis.

Activins ; genetics ; Animals ; Carbon Tetrachloride ; Follistatin ; Gene Expression ; Inhibin-beta Subunits ; genetics ; Liver Cirrhosis, Experimental ; chemically induced ; genetics ; pathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the roles of mouse erythroid differentiation and denucleation factor (MEDDF), a novel factor cloned in our laboratory recently, in erythroid terminal differentiation.

METHODSMouse erythroleukemia (MEL) cells were transfected with eukaryotic expression plasmid pcDNA-MEDDF. Then we investigated the changes on characteristics of cell growth by analyzing cells growth rate, mitotic index and colony-forming rate in semi-solid medium. The expressions of c-myc and beta-globin genes were analysed by semi-quantitative RT-PCR.

RESULTSMEL cells transfected with pcDNA-MEDDF showed significant lower growth rate, mitotic index, and colony-forming rate in semi-solid medium (P<0.01). The percentage of benzidine-positive cells was 32.8% after transfection. The expression of beta-globin in cells transfected with pcDNA-MEDDF was 3.43 times higher than that of control (MEL transfected with blank vector, pcDNA3.1), and the expression of c-myc decreased by 66.3%.

CONCLUSIONSMEDDF can induce differentiation of MEL cell and suppress its malignancy.

Activins ; genetics ; pharmacology ; Animals ; Cell Differentiation ; drug effects ; Cell Division ; drug effects ; Friend murine leukemia virus ; Globins ; biosynthesis ; genetics ; Inhibin-beta Subunits ; genetics ; pharmacology ; Leukemia, Erythroblastic, Acute ; metabolism ; pathology ; Mice ; Proto-Oncogene Proteins c-myc ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Transfection ; Tumor Cells, Cultured

BACKGROUND: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. METHODS: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. RESULTS: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. CONCLUSION: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.
Activin Receptors ; Activins ; Animals ; Benzamides ; Cell Proliferation ; Dendritic Cells ; Dioxoles ; Humans ; Macrophages ; Mice