Glycosaminoglycan synthesis and composition in human fibroblasts during in vitro cellular aging (IMR‐90)

Vogel, Kathryn G.; Kendall, Vaughan F.; Sapién, Robert

doi:10.1002/jcp.1041070214

Cited by 39 publications

(14 citation statements)

References 26 publications

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“…It has been known that undifferentiated cells are small in size and very proliferative, but differentiated cells are large in size and arrest their cell cycle (4, 35). Changes in the activity of synthesis and secretion of extracellular components, collagen and fibronectin, with age are controversial among authors (11,19,25,27,37). The relationship between the extent of differentiation and the activity of synthesis of extracellular substances has not been examined yet in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Organ‐Dependent Expression of Differentiated States in Fibroblasts Cultured in Vitro

Shimizu

Yoshizato

1992

Dev Growth Differ

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Mouse fibroblasts were obtained from three different organs (skin, lung and heart), cultured and investigated to know whether the fibroblasts express differentiated characters in an organ-dependent manner. Fibroblasts showed organ-dependent morphology at the confluent state. Fibroblasts were labeled with [35S]-methionine, and the pattern of protein synthesized was electrophoretically analyzed for both cellular proteins and extracellular proteins. Though most proteins were common to three types of fibroblasts, some proteins were produced in an organ-dependent manner. Experiments on DNA synthesis and colony forming ability under a low density culture revealed that skin fibroblasts were the most proliferative among the three, while heart fibroblasts were the least. When fibroblasts were three-dimensionally cultured in collagen gels, heart fibroblasts induced the gel contraction most intensely and skin fibroblasts did the least. In accordance with the ability of contraction heart fibroblasts secreted more collagen and fibronectin than skin and lung fibroblasts. Results in the present study indicate that the fibroblasts of three organs are in the organ-dependent states of differentiation; heart fibroblasts are well differentiated while skin and lung fibroblasts are less differentiated, ie., more proliferative and less active in the synthesis of extracellular matrices.

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Section: Discussionmentioning

confidence: 99%

Organ‐Dependent Expression of Differentiated States in Fibroblasts Cultured in Vitro

Shimizu

Yoshizato

1992

Dev Growth Differ

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“…With respect to the intracellular levels of heparan sulfate with antiproliferative activity, our observations are consistent with the presence of a large pool of minimally active heparan sulfate within the postconfluent SMCs and/or an accelerated destruction of mucopolysaccharide with growth inhibitory potency within the SMCs. In this regard, other investigators have observed that secreted and cell surface heparan sulfate are handled as separate metabolic pools in other cell types (29).…”

Section: Discussionmentioning

confidence: 99%

An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells.

Fritze¹,

Reilly²,

Rosenberg³

1985

The Journal of Cell Biology

311

144

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Heparan sulfate was isolated from the cell surface, cell pellet, and culture medium of exponentially growing as well as postconfluent bovine aortic smooth muscle cells (SMCs). After chromatography on DEAE-Sephadex and Sepharose 4B, the various mucopolysaccharides were examined for their ability to cause growth inhibition in a SMC bioassay. The heparan sulfate isolated from the surface of postconfluent SMCs possessed approximately eight times the antiproliferative potency per cell of the heparan sulfate obtained from the surface of exponentially growing SMCs. Heparan sulfate isolated from other fractions of exponentially growing or postconfluent SMCs possesses little growth inhibitory activity. The difference in the antiproliferative activities of heparan sulfate obtained from the surface of SMCs in the two growth states could not be attributed to the synthesis of a greater mass of mucopolysaccharide by postconfluent SMCs. Indeed, heparan sulfate isolated from the surface of the postconfluent SMCs exhibits a specific antiproliferative activity which is 13-fold greater than mucopolysaccharide obtained from the surface of exponentially growing SMCs and more than 40-fold greater than commercially available heparin. In addition, exponentially growing SMCs did not exhibit an enhanced ability to degrade the complex carbohydrate. Furthermore, other investigations indicate that the small amount of growth inhibitory activity intrinsic to heparan sulfate isolated from the surface of exponentially growing SMCs is due to residual, biologically active, mucopolysaccharide produced by the primary postconfluent SMCs from which the exponentially growing SMCs were derived. These studies suggest that bovine aortic SMCs are capable of controlling their own growth by the synthesis of a specific form of heparan sulfate with antiproliferative potency.Most connective tissues contain glycosaminoglycans as major components of their extracellular matrix. These high molecular weight, negatively charged sulfated mucopolysaccharides have been implicated in determining certain general overall properties of tissues such as hydration, elasticity, and permeability (1). It has also been suggested that glycosaminoglycans that are known to be associated with the surface of the cell could be involved in basic cellular functions, such as adhesion and motility (2, 3). However, little is known about whether specific structural elements on the glycosaminoglycans are responsible for the biologic properties of these components.Several investigators have demonstrated that the mucopolysaccharide, heparin, must satisfy unique structure-function relationships to interact with its protein co-factor, antithrombin, to alter allosterically the conformation of this protease inhibitor, and thereby accelerate neutralization of coagulation system enzymes (4). Our laboratory has recently shown that anticoagulantly active heparan sulfate molecules are present on the surface of endothelial cells and are, in part, responsible for maintaining the nonthrombogenic p...

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“…This is sustained by the observation that in other human fibroblasts, fibronectin production [24] and the secre tion of GAG [2,3] were also markedly re duced in cells that have been subjected to progressive subcultivation.…”

Section: Discussionmentioning

confidence: 71%

“…Therefore, it seems that these stromal cells did not present the morphological and cellu lar patterns which characterize in vitro-aged cells [22,23]. Early passage human embryo lung fibroblasts behave in a similar fashion and do not show significant changes in cell characteristics until they reach 30 CPD [2],…”

Section: Discussionmentioning

confidence: 97%

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Changes in Collagen Synthesis hy Human Bone Marrow Fibroblasts with Progressive Subcultivation

Fernández

Barahona²,

Martı́nez³

et al. 1989

Pathobiology

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Bone marrow fibroblasts from normal and leukemic patients were used to investigate the relationship between serial subcultivation and changes in collagen synthesis. A regime was established to generate subcultures up to 35 cumulative population doublings (CPDs) in normal cells and to 9 CPDs in leukemic cells. In both types of cells, collagen synthesis decreased as subcultivation progressed. In normal cells, collagen synthesis was reduced to 10% of the original levels at 18 CPDs and in leukemic cells at 8 CPDs. In normal fibroblasts, collagen synthesis was more profoundly affected than overall protein synthesis by subcultivation. In acute lymphoblastic leukemia-derived fibroblasts, the decrease in collagen synthesis paralleled that of total protein.

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Glycosaminoglycan synthesis and composition in human fibroblasts during in vitro cellular aging (IMR‐90)

Cited by 39 publications

References 26 publications

Organ‐Dependent Expression of Differentiated States in Fibroblasts Cultured in Vitro

Organ‐Dependent Expression of Differentiated States in Fibroblasts Cultured in Vitro

An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells.

Changes in Collagen Synthesis hy Human Bone Marrow Fibroblasts with Progressive Subcultivation

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