Follistatin regulates the relative proportions of endocrine versus exocrine tissue during pancreatic development

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
F. Miralles ◽  
P. Czernichow ◽  
R. Scharfmann
Keyword(s):  
Endocrine Cells ◽  
Glucose Transporter ◽  
Inductive Effect ◽  
Secretory Granules ◽  
Pancreatic Development ◽  
Soluble Factors ◽  
Repressive Effect ◽  
Development In Vitro

In this study, we have investigated the role of the embryonic mesenchyme in the development of the pancreas. We have compared the development in vitro of E12.5 rat pancreatic rudiments grown in the presence or absence of mesenchyme. When the E12.5 pancreatic epithelial rudiment is cultured in the presence of its surrounding mesenchyme, both morphogenesis and cytodifferentiation of the exocrine component of the pancreas are completely achieved, while only a few immature endocrine cells develop. The pancreatic rudiments grown in the absence of mesenchyme develop in a completely different way; the exocrine tissue develops poorly and fails to undergo acinar morphogenesis, while the endocrine tissue develops actively. Four times more insulin-positive cells develop after removal of the mesenchyme than in the cultures performed in the presence of mesenchyme. Moreover, the insulin-expressing cells developed in the mesenchyme-depleted rudiments appear mature since they do not coexpress glucagon, express the glucose transporter Glut-2 and express Rab3A, a molecule associated with the secretory granules. Moreover, these endocrine cells are able to associate and form true islets. Both the inductive effect of the mesenchyme on the proper development of the exocrine tissue and its repressive effect on the development of the endocrine cells are mediated by soluble factors. Follistatin, which is expressed by E12.5 pancreatic mesenchyme, can mimic both inductive and repressive effects of the mesenchyme. Follistatin could thus represent one of the mesenchymal factors required for the development of the exocrine tissue while exerting a repressive role on the differentiation of the endocrine cells.

scholarly journals circATP2A2 promotes osteosarcoma progression by upregulating MYH9

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1749-1761
Author(s):  
Xin Cao ◽  
Xianfeng Meng ◽  
Peng Fu ◽  
Lin Wu ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Area Under Curve ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Promising Target ◽  
Repressive Effect ◽  
Cell Malignancy

Abstract Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

Role of mesenchymal nidogen for epithelial morphogenesis in vitro

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 2003-2014 ◽  
Author(s):  
P. Ekblom ◽  
M. Ekblom ◽  
L. Fecker ◽  
G. Klein ◽  
H.Y. Zhang ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Northern Blotting ◽  
Epithelial Morphogenesis ◽  
Extracellular Matrix Protein ◽  
Epithelial Development ◽  
Morphogenesis In Vitro ◽  
Development In Vitro ◽  
Membrane Components

Recent biochemical studies suggested that the extracellular matrix protein nidogen is a binding molecule linking together basement membrane components. We studied its expression and role during development. By immunofluorescence and northern blotting, nidogen was found early during epithelial cell development of kidney and lung. Yet, in situ hybridization revealed that nidogen was not produced by epithelium but by the adjacent mesenchyme in both organs. Binding of mesenchymal nidogen to epithelial laminin may thus be a key event during epithelial development. This is supported by antibody perturbation experiments. Antibodies against the nidogen binding site on laminin B2 chain perturbed epithelial development in vitro in embryonic kidney and lung. Mesenchymal nidogen could be important for early stages of epithelial morphogenesis.

scholarly journals Role of β-Catenin Activation Levels and Fluctuations in Controlling Cell Fate

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 176 ◽  
Author(s):  
Elisa Pedone ◽  
Lucia Marucci
Keyword(s):  
Signaling Pathway ◽  
Cell Fate ◽  
Temporal Dynamics ◽  
Cellular Systems ◽  
Future Research ◽  
Somatic Cell Reprogramming ◽  
Development In Vitro ◽  
Pluripotency Maintenance

Cells have developed numerous adaptation mechanisms to external cues by controlling signaling-pathway activity, both qualitatively and quantitatively. The Wnt/β-catenin pathway is a highly conserved signaling pathway involved in many biological processes, including cell proliferation, differentiation, somatic cell reprogramming, development, and cancer. The activity of the Wnt/β-catenin pathway and the temporal dynamics of its effector β-catenin are tightly controlled by complex regulations. The latter encompass feedback loops within the pathway (e.g., a negative feedback loop involving Axin2, a β-catenin transcriptional target) and crosstalk interactions with other signaling pathways. Here, we provide a review shedding light on the coupling between Wnt/β-catenin activation levels and fluctuations across processes and cellular systems; in particular, we focus on development, in vitro pluripotency maintenance, and cancer. Possible mechanisms originating Wnt/β-catenin dynamic behaviors and consequently driving different cellular responses are also reviewed, and new avenues for future research are suggested.

scholarly journals Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

2013 ◽  
Vol 24 (15) ◽  
pp. 2389-2397 ◽  
Author(s):  
Jennifer Roccisana ◽  
Jessica B. A. Sadler ◽  
Nia J. Bryant ◽  
Gwyn W. Gould
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Vitro Assay ◽  
Protein Receptor ◽  
Storage Vesicles ◽  
Storage Vesicle ◽  
Impaired Insulin ◽  
Endosomal Pathway

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target–soluble N-ethylmaleimide–sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using sub­cellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.

The Toll-Like Receptor-Like Molecule CD180 and Soluble CD14 Transmit Survival Signals in B-Cell Chronic Lymphocytic Leukemia Cells Presumably by Acting As Co-Receptors,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3883-3883
Author(s):  
Martina Seiffert ◽  
Angela Schulz ◽  
Stephan Stilgenbauer ◽  
Peter Lichter
Keyword(s):  
Intracellular Signaling ◽  
Surface Expression ◽  
Lymphocytic Leukemia ◽  
Toll Like Receptor ◽  
Soluble Cd14 ◽  
Soluble Factors ◽  
Cell Chronic Lymphocytic Leukemia ◽  
Survival Signals

Abstract Abstract 3883 Survival and proliferation of B-cell chronic lymphocytic leukemia (CLL) cells strongly depend on external factors. When removed from their natural microenvironment CLL cells rapidly undergo spontaneous apoptosis in vitro unless cocultured with stromal cells or non-malignant leukocytes. Recently, we could show that monocytes effectively support long-term survival of CLL cells in vitro. Our results from cytokine antibody arrays and extensive transcriptome analyses of primary CLL cell cocultures suggested a functional role of several soluble factors as well as signaling pathways of innate immunity, like Toll-like receptor-, TREM1- and NRF2-mediated signaling. The most interesting soluble factors are currently quantified in serum samples of the german CLL8 study cohort of CLL patients by cytometric bead arrays. So far, our data show that two of these candidates, CCL2 and soluble CD14, are significantly increased in the serum of CLL patients. In vitro studies using recombinant soluble CD14 demonstrated that CLL cell survival was significantly increased in the presence of this factor. CD14 which is expressed in particular by monocytes and macrophages is an important mediator of innate immunity. Along with TLR-4, CD14 acts as a co-receptor for the detection of bacterial lipopolysaccharide (LPS). Alternatively, LPS can also bind to the toll-like receptor-like molecule CD180, which shows strong homology to TLR-4, but does not harbor an intracellular signaling domain. Since TLR-4 is not expressed in CLL cells, we investigated the potential role of CD180 in CD14-mediated cell survival. Flow cytometry analysis revealed an upregulation of CD180 surface expression in CLL cells under survival-inducing culture conditions. Stimulation of CD180 with a cross-linking antibody resulted in activation of CLL cells measured by increased cell size and upregulation of the activation marker CD86, and significantly increased survival rates of CLL cells. Both CD14- and CD180-mediated survival signals lead to an increase in NF-κB activity and up-regulation of its target gene BCL-2. Depletion of CD180 surface expression in CLL cells abolished the pro-survival effect of soluble CD14, suggesting that this factor mediates its signals via binding to CD180. In summary, our data demonstrate that both, soluble CD14 and the toll-like receptor-like molecule CD180 transmit pro-survival signals in CLL cells, most likely by acting as co-receptors. Currently, we characterize the intracellular signaling machinery which is involved in these processes. Disclosures: No relevant conflicts of interest to declare.

Comparison of Murine Embryonic Pancreatic Development in Vitro and in Vivo

Pancreas ◽  
2011 ◽  
Vol 40 (7) ◽  
pp. 1012-1017 ◽  
Author(s):  
Fengxia Ma ◽  
Cécile Haumaitre ◽  
Fang Chen ◽  
Zhongchao Han
Keyword(s):  
Pancreatic Development ◽  
Development In Vitro

scholarly journals Deciphering the role of miR-71 in Echinococcus multilocularis early development in vitro

2019 ◽  
Vol 13 (12) ◽  
pp. e0007932 ◽  
Author(s):  
Matías Gastón Pérez ◽  
Markus Spiliotis ◽  
Natalia Rego ◽  
Natalia Macchiaroli ◽  
Laura Kamenetzky ◽  
...  
Keyword(s):  
Early Development ◽  
Echinococcus Multilocularis ◽  
Development In Vitro

scholarly journals The role of organ level conditioning on the promotion of engineered heart valve tissue development in-vitro using mesenchymal stem cells

Biomaterials ◽  
2010 ◽  
Vol 31 (6) ◽  
pp. 1114-1125 ◽  
Author(s):  
Sharan Ramaswamy ◽  
Danielle Gottlieb ◽  
George C. Engelmayr ◽  
Elena Aikawa ◽  
David E. Schmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heart Valve ◽  
Tissue Development ◽  
Valve Tissue ◽  
Heart Valve Tissue ◽  
Organ Level ◽  
Development In Vitro

Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase–1 expression in murine microglia by glioma-derived soluble factors

2008 ◽  
Vol 108 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Yoshiteru Nakano ◽  
Etsushi Kuroda ◽  
Tomohiro Kito ◽  
Satoshi Uematsu ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Soluble Factors ◽  
Arachidonate Cascade ◽  
Cox Inhibitor ◽  
Murine Microglia ◽  
The Central Nervous System

Object Microglia are one of the members of monocyte/macrophage lineage in the central nervous system (CNS) and exist as ramified microglia in a normal resting state, but they are activated by various stimuli, such as tumors. Activated microglia induce immune responses in the CNS, but the precise functions of microglia in glioma microenvironments are not clear. It has been reported that glioma cells produce prostaglandin (PG)E2, which promotes the growth of tumor cells and possesses immunosuppressive activity. The authors previously reported that PGE2 production by peritoneal macrophages was enhanced by glioma-derived soluble factors, which induce an immunosuppressive state. In this study, they investigated PGE2 production by microglia treated with glioma cells and assessed the role of microglia in glioma microenvironments in the mouse. Methods Microglia and peritoneal macrophages were cultured in vitro with or without lipopolysaccharide, and tumor necrosis factor (TNF) and PGE2 in the culture supernatant were measured using L929 bioassay and enzyme immunoassay. The expression of mRNA was measured using reverse transcriptase polymerase chain reaction, and the protein expression was assayed with Western blotting. In some experiments glioma cells and conditioned glioma medium were added to the microglia cultures. Results Glioma cells studied in this report did not produce a significant amount of PGE2. However, the coculture of microglia with glioma cells or conditioned glioma medium led to the production of a large amount of PGE2. The enhancement of PGE2 production by microglia was more significant than that by peritoneal macrophages. The expression of cyclooxygenase (COX)–2 and particularly the expression of microsomal PGE synthase (mPGES)–1 (a terminal enzyme of the arachidonate cascade) in microglia were enhanced by conditioned glioma medium. The enhancement of mPGES-1 expression in microglia was more significant than that in peritoneal macrophages. The production of TNF was suppressed when culturing microglia with conditioned glioma medium, but this suppression was abrogated by the addition of a COX inhibitor (NS-398) and a PGE2 receptor (EP4) antagonist. Furthermore, TNF production was not suppressed in microglia from mPGES-1–deficient mice. Conclusions These results indicate that PGE2 production by microglia is enhanced by conditioned glioma medium, which induces an immunosuppressive state in the CNS. Therefore, the manipulation of microglia, from the standpoint of PGE2, provides investigators with an important strategy to induce an effective antiglioma immune response.

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