Global ETD Search

11	The effects of bone morphogenic proteins and transforming growth factor [beta] on in-vitro endothelin-1 production by human pulmonary microvascular endothelial cells / Star, Gregory. January 2008 (has links) No description available. Lung -- metabolism. Endothelium, Vascular -- metabolism. Endothelin-1 -- biosynthesis.
12	MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes Ahmed, Mohammed I., Mardaryev, Andrei N., Lewis, Christopher J., Sharov, A.A., Botchkareva, Natalia V. 17 June 2011 (has links) Yes / Bone morphogenetic proteins (BMPs) play essential roles in the control of skin development, postnatal tissue remodelling and tumorigenesis. To explore whether some of the effects of BMP signalling are mediated by microRNAs, we performed genome-wide microRNA (miRNA) screening in primary mouse keratinocytes after BMP4 treatment. Microarray analysis revealed substantial BMP4-dependent changes in the expression of distinct miRNAs, including miR-21. Real-time PCR confirmed that BMP4 dramatically inhibits miR-21 expression in the keratinocytes. Consistently, significantly increased levels of miR-21 were observed in transgenic mice overexpressing the BMP antagonist noggin under control of the K14 promoter (K14-noggin). By in situ hybridization, miR-21 expression was observed in the epidermis and hair follicle epithelium in normal mouse skin. In K14-noggin skin, miR-21 was prominently expressed in the epidermis, as well as in the peripheral portion of trichofolliculoma-like hair follicle-derived tumours that contain proliferating and poorly differentiated cells. By transfecting keratinocytes with a miR-21 mimic, we identified the existence of two groups of the BMP target genes, which are differentially regulated by miR-21. These included selected BMP-dependent tumour-suppressor genes (Pten, Pdcd4, Timp3 and Tpm1) negatively regulated by miR-21, as well as miR-21-independent Id1, Id2, Id3 and Msx2 that predominantly mediate the effects of BMPs on cell differentiation. In primary keratinocytes and HaCaT cells, miR-21 prevented the inhibitory effects of BMP4 on cell proliferation and migration. Thus, our study establishes a novel mechanism for the regulation of BMP-induced effects in the skin and suggests miRNAs are important modulators of the effects of growth factor signalling pathways on skin development and tumorigenesis. Animals Bone morphogenetic protein 4 Carrier proteins Cell transformation Cells Epidermis Gene expression regulation Neoplastic Genes Tumor suppressor Genome-wide association study Keratin-14 Keratinocytes Mice Inbred strains Transgenic MicroRNAs Microarray analysis Morphogenesis Signal transduction REF 2014
13	Bone morphogenetic proteins differentially regulate pigmentation in human skin cells Singh, Suman K., Abbas, Waqas A., Tobin, Desmond J. January 2012 (has links) No / Bone morphogenetic proteins (BMPs) are a large family of multi-functional secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by downregulating tyrosinase expression and activity in epidermal melanocytes. However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in melanocytes and keratinocytes in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully matched primary cultures of adult human melanocytes and keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in melanocytes, which was associated with increased melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in melanocytes behaviour. Adult Aged Bone Morphogenetic Protein 4 Antagonists & inhibitors Metabolism Pharmacology Bone Morphogenetic Protein 6 Antagonists & inhibitors Metabolism Pharmacology Bone Morphogenetic Protein Receptors Coculture techniques Epidermis Drug effects Radiation effects Female Gene knockdown techniques Humans Keratinocytes Enzymology Melanins Biosynthesis Melanocytes Ultrastructure Middle aged Models Biological Monophenol Monooxygenase Myosins Pigmentation Pseudopodia Signal transduction Skin cytology Smad Proteins Ultraviolet rays Up-Regulation p38 Mitogen-Activated Protein Kinases REF 2014

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