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1.
Biochem Soc Trans ; 34(Pt 3): 454-5, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16709185

RESUMO

HS (heparan sulphate) plays a key role in angiogenesis, by interacting with growth factors required in the process. It has been proposed that HS controls the diffusion, and thus the availability, of platelet-derived growth factor B that is needed for pericyte recruitment around newly formed capillaries. The present paper summarizes our studies on the importance of HS structure in this regulatory process.


Assuntos
Movimento Celular/fisiologia , Heparitina Sulfato/fisiologia , Pericitos/fisiologia , Proteínas Proto-Oncogênicas c-sis/fisiologia , Animais , Humanos , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo
2.
Nat Cell Biol ; 2(5): 302-9, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10806482

RESUMO

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.


Assuntos
Endopeptidases/metabolismo , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Animais , Células COS , Células Epiteliais/química , Células Epiteliais/enzimologia , Expressão Gênica/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Hibridização In Situ , Insetos , Rim/química , Rim/embriologia , Rim/enzimologia , Ligantes , Linfocinas , Mesoderma/química , Mesoderma/enzimologia , Camundongos , Dados de Sequência Molecular , Miocárdio/química , Miocárdio/enzimologia , Fator de Crescimento Derivado de Plaquetas/química , Fator de Crescimento Derivado de Plaquetas/farmacologia , Estrutura Terciária de Proteína , RNA Mensageiro/análise , Coelhos , Homologia de Sequência de Aminoácidos , Transgenes/fisiologia
3.
Development ; 126(14): 3047-55, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10375497

RESUMO

Development of a vascular system involves the assembly of two principal cell types - endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) - into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B-/- and PDGFR-beta-/- embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B-/- embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-beta-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.


Assuntos
Vasos Sanguíneos/embriologia , Músculo Liso Vascular/metabolismo , Pericitos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Actinas/metabolismo , Animais , Artérias/embriologia , Artérias/metabolismo , Artérias/patologia , Vasos Sanguíneos/citologia , Vasos Sanguíneos/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Divisão Celular , Movimento Celular , Desmina/metabolismo , Camundongos , Camundongos Endogâmicos , Camundongos Mutantes , Músculo Liso Vascular/citologia , Músculo Liso Vascular/embriologia , Pericitos/citologia , Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-sis , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Receptores do Fator de Crescimento Derivado de Plaquetas/genética
4.
Development ; 126(3): 457-67, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9876175

RESUMO

There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors.


Assuntos
Sistema Nervoso Central/embriologia , Bainha de Mielina/fisiologia , Oligodendroglia/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Animais , Encéfalo/embriologia , Diferenciação Celular , Divisão Celular , Camundongos , Camundongos Knockout , Proteína Proteolipídica de Mielina/fisiologia , Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Proto-Oncogênicas c-sis , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Receptores do Fator de Crescimento Derivado de Plaquetas/fisiologia
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