Opposing regulation of cell proliferation by retinoic acid and the serotonin 2B receptor in the mouse frontonasal mass

Homeobox (Hox) genes encode a family of transcription factors that regulate embryonic patterning and organogenesis. In embryos, alterations of the normal pattern of Hox gene expression result in homeotic transformations and malformations. Disruption of theHoxa1gene, the most 3′ member of the Hoxa cluster and a retinoic acid (RA) direct target gene, results in abnormal ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal death. We have generated Hoxa1-/-embryonic stem (ES) cells (named Hoxa1-15) from Hoxa1-/-mutant blastocysts to study the Hoxa1 signaling pathway. We have characterized in detail these Hoxa1-/-ES cells by performing microarray analyses, and by this technique we have identified a number of putative Hoxa-1 target genes, including genes involved in bone development (e.g. Col1a1,Postn/Osf2, and the bone sialoprotein gene orBSP), genes that are expressed in the developing brain (e.g. Nnat,Wnt3a,BDNF,RhoB, andGbx2), and genes involved in various cellular processes (e.g. M-RAS,Sox17,Cdkn2b,LamA1,Col4a1,Foxa2,Foxq1,Klf5, andIgf2). Cell proliferation assays and Northern blot analyses of a number of ES cell markers (e.g. Rex1,Oct3/4,Fgf4, andBmp4) suggest that the Hoxa1 protein plays a role in the inhibition of cell proliferation by RA in ES cells. Additionally, Hoxa1-/-ES cells express high levels of various endodermal markers, includingGata4andDab2, and express much lessFgf5after leukemia inhibitory factor (LIF) withdrawal. Finally, we propose a model in which the Hoxa1 protein mediates repression of endodermal differentiation while promoting expression of ectodermal and mesodermal characteristics.

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Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2015.v34.96-103 ◽

2015 ◽

Vol 34 (2) ◽

pp. 96

Author(s):

Linda Yuliati ◽

Etik Mardliyati ◽

Kusmarinah Bramono ◽

Hans Joachim Freisleben

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Retinoic Acid ◽

Collagen Synthesis ◽

Active Agent ◽

Dermal Fibroblasts ◽

Type Iii Collagen ◽

Type I ◽

Human Dermal Fibroblasts ◽

Type Iii

Background Asiatiocoside, a saponin component isolated from Centella asiatica can improve wound healing by promoting the proliferation of human dermal fibroblasts (HDF) and synthesis of collagen. The skin-renewing cells and type I and III collagen synthesis decrease with aging, resulting in the reduction of skin elasticity and delayed wound healing. Usage of natural active compounds from plants in wound healing should be evaluated and compared to retinoic acid as an active agent that regulates wound healing. The aim of this study was to compare and evaluate the effect of asiaticoside and retinoic acid to induce greater cell proliferation and type I and III collagen synthesis in human dermal fibroblast. Methods Laboratory experiments were conducted using human dermal fibroblasts (HDF) isolated from human foreskin explants. Seven passages of HDF were treated with asiaticoside and retinoic acid at several doses and incubated for 24 and 48 hours. Cell viability in all groups was tested with the MTT assay to assess HDF proliferation. Type I and III collagen synthesis was examined using the respective ELISA kits. Analysis of variance was performed to compare the treatment groups. Results Asiaticoside had significantly stronger effects on HDF proliferation than retinoic acid (p<0.05). The type III collagen production was significantly greater induction with asiaticoside compared to retinoic acid (p<0.05). Conclusion Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

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Retinoic acid decreases fetal lung mesenchymal cell proliferation in vivo and in vitro

Development Growth & Differentiation ◽

10.1111/j.1440-169x.2004.00745.x ◽

2004 ◽

Vol 46 (3) ◽

pp. 275-282 ◽

Cited By ~ 7

Author(s):

Sussie Dalvin ◽

Katsumi Komatsuzaki ◽

Mark A. Anselmo ◽

David E. Kling ◽

Jay J. Schnitzer ◽

...

Keyword(s):

Cell Proliferation ◽

Retinoic Acid ◽

Mesenchymal Cell ◽

Fetal Lung

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Inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell proliferation

World Journal of Gastroenterology ◽

10.3748/wjg.v9.i9.2117 ◽

2003 ◽

Vol 9 (9) ◽

pp. 2117 ◽

Cited By ~ 6

Author(s):

Yun-Feng Piao

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Retinoic Acid ◽

Carcinoma Cell ◽

Inhibitory Effect ◽

Human Hepatocellular Carcinoma ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Human Hepatocellular Carcinoma Cell ◽

Hepatocellular Carcinoma Cell

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Retinoic acid modulation of the early development of the inner ear is associated with the control of c-fos expression

Development ◽

10.1242/dev.110.4.1081 ◽

1990 ◽

Vol 110 (4) ◽

pp. 1081-1090 ◽

Cited By ~ 2

Author(s):

J. Represa ◽

A. Sanchez ◽

C. Miner ◽

J. Lewis ◽

F. Giraldez

Keyword(s):

Cell Proliferation ◽

Retinoic Acid ◽

Inner Ear ◽

Early Development ◽

Otic Vesicle ◽

Low Concentrations ◽

Full Effect ◽

20 Nm ◽

Otic Vesicles

The effects of retinoic acid (RA) on the early development of the inner ear were studied in vitro using isolated chick embryo vesicles. Low concentrations of RA (1–50 nM) inhibited vesicular growth in stage 18 otic vesicles that were made quiescent and then reactivated by either serum or bombesin. Growth inhibition was concentration-dependent and was paralleled by a reduction in the rate of DNA synthesis as measured by [3H]thymidine incorporation. Half-inhibition occurred between 1 and 10 nM RA, and the full effect at 20 nM. Retinoic acid, in the presence of serum, induced the precocious differentiation of (1) secretory epithelium, the tegmentum vasculosum and endolymphatic sac and (2) early sensory and supporting epithelia. These structures were positioned in their corresponding normal presumptive areas. The overall direction of growth was reversed by RA and the ratio of the internal to the external vesicular surface area increased with RA concentration. The expression of the nuclear proto-oncogene c-fos in the developing otic vesicle was transient and stage-dependent. High levels of c-fos mRNA were positively correlated with cell proliferation. Incubation of growth-arrested otic vesicles with bombesin plus insulin at concentrations that induced cell proliferation produced a strong induction of c-fos. This mitogen-induced expression was suppressed by 25 nM RA. The results suggest (1) a role for retinoic acid in controlling the early development of the inner ear and (2) that this control is effected through the regulation of the proto-oncogene c-fos.

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Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.275.1.l71 ◽

1998 ◽

Vol 275 (1) ◽

pp. L71-L79 ◽

Cited By ~ 11

Author(s):

Elodie Nabeyrat ◽

Valérie Besnard ◽

Sophie Corroyer ◽

Véronique Cazals ◽

Annick Clement

Keyword(s):

Cell Proliferation ◽

Retinoic Acid ◽

Growth Factor ◽

Alveolar Epithelium ◽

Cell Number ◽

Dependent Manner ◽

Alveolar Epithelial ◽

Igf System ◽

Tgf Β1

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-β1. These results together with the known stimulatory effect of TGF-β1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-β1 pathway.

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