Inhibiting effect of procollagen peptides on collagen biosynthesis in fibroblast cultures.

Wiestner, Manfred; Krieg, T; Hörlein, D; Glanville, Robert W.; Fietzek, Peter P.; Müller, Peter

doi:10.1016/s0021-9258(18)50277-5

Cited by 244 publications

(21 citation statements)

References 37 publications

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“…The processing of procollagen is an important event in collagen fibril assembly, and the procollagen propeptides have been implicated in the regulation of collagen fibril formation, as well as the quantity of collagen synthesized (35). In vivo and in vitro the processing of the propeptides has been suggested to be associated with the control of fibril diameter (8,9,20,21).…”

Section: Discussionmentioning

confidence: 99%

Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation.

Birk¹,

Trelstad²

1986

The Journal of Cell Biology

341

235

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Abstract. The formation of collagen fibrils, fibril bundies, and tissue-specific collagen macroaggregates by chick embryo tendon fibroblasts was studied using conventional and high voltage electron microscopy. During chick tendon morphogenesis, there are at least three extraceUular compartments responsible for three levels of matrix organization: collagen fibrils, bundles, and collagen macroaggregates. Our observations indicate that the initial extracellular events in collagen fibrillogenesis occur within narrow cytoplasmic recesses, presumably under close cellular regulation. Collagen fibrils are formed within these deep, narrow recesses, which are continuous with the extracellular space. Where these narrow recesses fuse with the cell surface, it becomes highly convoluted with folds and processes that envelope forming fibril bundles. The bundles laterally associate and coalesce, forming aggregates within a third cell-defined extracellular compartment. Our interpretation is that this third compartment forms as cell processes retract and cytoplasm is withdrawn between bundles. These studies define a hierarchical organization within the tendon, extending from fibril assembly to fascicle formation. Correlation of different levels of extracellular compartmentalization with tissue architecture provides insight into the cellular controls involved in collagen fibril and higher order assembly and a better understanding of how collagen fibrils are collected into structural groups, positioned, and woven into functional tissue-specific collagen macroaggregates.

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Section: Discussionmentioning

confidence: 99%

Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation.

Birk¹,

Trelstad²

1986

The Journal of Cell Biology

341

235

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“…The resulting pNcollagen (that is, the mature collagen with the Npropeptide attached) assembles into small diameter fibrils with regular borders 39,40 . Retention of the Npropeptide in the collagen molecule might also compromise the intracellular functions of the pro peptide, such as protein phosphorylation, collagen synthesis and cell adhesion 41,42 . Furthermore, the Npropeptide in the extracellular matrix binds to specific cytokines (for example, transforming growth factorβ1 (TGFβ1) and BMP2), which are crucial for bone development 42 .…”

Section: Structural and Quantitative Collagen Defectsmentioning

confidence: 99%

Osteogenesis Imperfecta

Marini¹

2010

Management of Genetic Syndromes

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Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

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“…The procollagen-like region of TSP1 consists of "~90 residues, including 10 cysteines, that are homologous to the 10.7-kD propeptide that is cleaved from the NH2 terminus of human collagen I during maturation of the collagen fibril (Vuorio and de Crombrugghe, 1990). This collagen propeptide can selectively downregulate synthesis of the prood and proof2 chains of collagen I (Wiestner et al, 1979). The fact that many diverse inhibitors of angiogenesis have in common the ability to interfere with collagen synthesis and/or deposition (Ingber and Folkman, 1988;Maragoudakis et al, 1988) led us to test the procollagen homology region of TSP1 for inhibitory activity.…”

Section: Peptides Derived From the Procollagen Homology Region Of Tspi Block Neovascularizationmentioning

confidence: 99%

Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity

Tolsma

Volpert

Good³

et al. 1993

The Journal of Cell Biology

529

407

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Abstract. Thrombospondin-1 (TSP1) is a large modular matrix protein containing three identical disulfidelinked 180-kD chains that inhibits neovascularization in vivo (Good et al., 1990). To determine which of the structural motifs present in the 180-kD TSP1 polypeptide mediate the anti-angiogenic activity, a series of protease-generated fragments were tested using several in vitro and in vivo assays that reflect angiogenic activity. The majority of the anti-angiogenic activity of TSP1 resides in the central 70-kD stalk region which alone could block neovascularization induced by bFGF in the rat cornea in vivo and inhibit both migration in a modified Boyden chamber and [~H]thymidine incorporation stimulated by bFGF in cultured capillary endothelial cells. Although TSP1 has been shown to bind active TGF/31, this cytokine could not account for the inhibitory effects of the stalk region of TSP1 on cultured endothelial cells.Peptides and truncated molecules were used to further localize inhibitory activity to two domains of the central stalk, the procollagen homology region and the properdin-like type 1 repeats. Trimeric recombinant TSP1 containing NH2-terminal sequences truncated after the procollagen-like module inhibited endothelial cell migration in vitro and corneal neovascularization in vivo whereas trimeric molecules truncated before this domain were inactive as was the NH2-terminal heparin-binding domain that is present in both recombinant molecules. A series of peptides from the procollagen-like region, the smallest of which consisted of residues 303-309 of TSP1, inhibited angiogenesis in vivo in the rat cornea and the migration of endothelial cells in vitro. A 19-residue peptide containing these sequences blocked vessel formation in the granulation tissue invading a polyvinyl sponge implanted into the mouse. Nineteen residue peptides derived from two of the three type 1 repeats present in the intact TSP1 molecule blocked neovascularization in vivo in the rat cornea and inhibited the migration of cultured endothelial cells with EDs0'S of 0.6-7 #M. One of these peptides, containing residues 481-499 of TSP1, also inhibited vessel formation in granulation tissue invading sponges in vivo.These results suggest that the large TSP1 molecule employs at least two different structural domains and perhaps two different mechanisms to accomplish a sin 2 gle physiological function, the inhibition of neovascularization. The definition of short peptides from each of these domains that are able to block the angiogenic process may be of use in designing targeted inhibitors of the pathological neovascularization that underlies many diseases.

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Inhibiting effect of procollagen peptides on collagen biosynthesis in fibroblast cultures.

Cited by 244 publications

References 37 publications

Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation.

Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation.

Osteogenesis Imperfecta

Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity

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