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Retinoic Acid Treatment (retinoic + acid_treatment)
Selected AbstractsVascular regression is required for mesenchymal condensation and chondrogenesis in the developing limbDEVELOPMENTAL DYNAMICS, Issue 3 2001Melinda Yin Abstract Vascular regression occurs during limb mesenchymal cell condensation and chondrogenesis, but it is unclear whether it is required for these processes or is a secondary phenomenon without major regulatory roles. To address this issue, beads presoaked with the potent angiogenic factor vascular endothelial growth factor (VEGF) were implanted in the vicinity of the prospective digit 2 in early chick embryo wing buds and the effects on angiogenesis and digit development were determined over time. We found that VEGF treatment caused a marked local increase in blood vessel number and density. Strikingly, this was accompanied by inhibition of digit 2 development as revealed by lack of expression of chondrogenic transcription factor Sox9 and absence of Alcian blue staining. Vascular distribution and skeletal development in adjacent areas remained largely unaffected. Inhibition of digit formation and excess vascularization were both reversible upon further embryonic growth and dissipation of VEGF activity. When supernumerary digits were induced at the anterior limb margin by retinoic acid treatment, their development was also preceded by vascular regression; interestingly, cotreatment with VEGF inhibited supernumerary digit development as well. Direct exposure of limb mesenchymal cells in micromass cultures to VEGF caused no obvious effects on condensation and chondrogenesis, indicating that VEGF effects are not due to direct action on skeletal cells. Our results are the first to provide evidence that vascular regression is required for mesenchymal condensation and chondrogenesis. A model of how patterning mechanisms and vascular regression may intersect and orchestrate limb skeletogenesis is proposed. © 2001 Wiley-Liss, Inc. [source] Presenilin 1 mediates retinoic acid-induced differentiation of SH-SY5Y cells through facilitation of Wnt signalingJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Kengo Uemura Abstract Presenilin 1 interacts with ,-catenin, an essential component of the Wnt signaling pathway. To elucidate the role of presenilin 1-,-catenin interaction in neuronal differentiation, we established SH-SY5Y cells stably expressing wild-type presenilin 1, P117L mutant presenilin 1, which is linked to the early-onset familial form of Alzheimer's disease, and D385A mutant presenilin 1, which has no aspartyl proteinase activity. We demonstrate that SH-SY5Y cells stably expressing D385A mutant presenilin 1 failed to differentiate in response to retinoic acid treatment. Retinoic acid caused an increase in nuclear ,-catenin levels in SH-SY5Y cells, which was followed by an increase in cyclin D1 protein levels. Abnormal cellular accumulation of ,-catenin was observed in D385A mutant transfected cells, whereas nuclear ,-catenin and cellular cyclin D1 levels failed to increase. Conversely, SH-SY5Y cells expressing the P117L mutant differentiated normally and showed increased nuclear ,-catenin and cellular cyclin D1 levels. These findings suggest that neuronal differentiation of SH-SY5Y cells involves the Wnt signaling pathway and that presenilin 1 plays a crucial role in Wnt signal transduction by regulating the nuclear translocation of ,-catenin. © 2003 Wiley-Liss, Inc. [source] Angiogenesis in skin aging and photoagingTHE JOURNAL OF DERMATOLOGY, Issue 9 2007Jin Ho CHUNG ABSTRACT Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process. [source] Cholinergic switch associated with morphological differentiation in neuroblastoma,THE JOURNAL OF PATHOLOGY, Issue 4 2009Franck Bourdeaut Abstract The morphology of malignant cells distinguishes between undifferentiated, poorly differentiated and differentiating neuroblastomas and constitutes a strong prognostic factor. Spontaneous or treatment-induced maturation characterizes a subset of neuroblastomas. It constitutes the basis of retinoic acid treatment to improve survival in aggressive neuroblastomas. However, the molecular events that drive differentiation are poorly understood. In the present study we have investigated the relationships between gene expression profiles and differentiation criteria in stroma-poor neuroblastomas. This study included three undifferentiated (UN), 20 poorly differentiated (PDN) and 11 differentiating (DN) neuroblastomas. These groups could be clearly separated using unsupervised clustering methods, which further enabled a major classification impact of genes involved in neural development, differentiation and function to be identified. UNs are characterized by high ASCL1, high PHOX2B, low GATA2, low TH and low DBH expressions. Most PDNs harbour a clear adrenergic phenotype, even in the presence of missense PHOX2B mutations. Finally, all DN tumours demonstrate cholinergic features. Depending upon their association with adrenergic characteristics, this enables dual ,cholinergic/adrenergic' and ,fully cholinergic' neuroblastomas to be defined. This suggests that the cholinergic switch, a final specification process that occurs physiologically in a minority of sympathetic neurons, is a critical step of differentiation in some neuroblastic tumours. This switch is associated with a down regulation of DBH that is apparently not strictly dependent upon PHOX2B. Conversely, GATA2 and TFAP2B may play critical roles in maintaining adrenergic features in poorly differentiated tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||