A substrate of the cell-attachment sequence of fibronectin (Arg-Gly-Asp-Ser) is sufficient to promote transition of arterial smooth muscle cells from a contractile to a synthetic phenotype

Hedin, Ulf; Bottger, Bradford A.; Luthman, Johan; Johansson, Staffan; Thyberg, Johan

doi:10.1016/0012-1606(89)90052-3

Cited by 98 publications

(49 citation statements)

References 39 publications

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“…Recently, Yoshii and Oka (59) reported that collagen type-I-derived filaments guided peripheral nerve regeneration. Fibronectin, another important component of the ECM, integrates with the receptors of the integrin family and modulates many basic cellular functions, including cell adhesion, migration, cell growth, differentiation, and programmed cell death (1,19,20,22,24,60). Fibronectin stimulates nerve fiber growth in culture (10).…”

Section: Discussionmentioning

confidence: 99%

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Zhao

Duan

Reyes

et al. 2002

Experimental Neurology

763

468

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There is now evidence to suggest that bone marrow mesenchymal stem cells (MSCs) not only differentiate into mesodermal cells, but can also adopt the fate of endodermal and ectodermal cell types. In this study, we addressed the hypotheses that human MSCs can differentiate into neural cells when implanted in the brain and restore sensorimotor function after experimental stroke. Purified human MSCs were grafted into the cortex surrounding the area of infarction 1 week after cortical brain ischemia in rats. Two and 6 weeks after transplantation animals were assessed for sensorimotor function and then sacrificed for histological examination. Ischemic rats that received human MSCs exhibited significantly improved functional performance in limb placement test. Histological analyses revealed that transplanted human MSCs expressed markers for astrocytes (GFAP ؉ ), oligodendroglia (GalC ؉ ), and neurons (␤III ؉ , NF160 ؉ , NF200 ؉ , hNSE ؉ , and hNF70 ؉ ). The morphological features of the grafted cells, however, were spherical in nature with few processes. Therefore, it is unlikely that the functional recovery observed by the ischemic rats with human MSC grafts was mediated by the integration of new "neuronal" cells into the circuitry of the host brain. The observed functional improvement might have been mediated by proteins secreted by transplanted hMSCs, which could have upregulated host brain plasticity in response to experimental stroke.

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Section: Discussionmentioning

confidence: 99%

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Zhao

Duan

Reyes

et al. 2002

Experimental Neurology

763

468

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“…[25][26][27] FN mediates attachment and spreading and initiates a structural reorganization of the cells to the synthetic phenotype. 25 In contrast, laminin and collagen type IV promote the contractile phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…25,27 FN was found to exert its effect via the cell attachment sequence Arg-Gly-Asp and by interaction with a cell surface receptor belonging to the integrin family of proteins. 28 Hedin et al 26 demonstrated that a substrate composed of the cell attachment sequence of FN (Arg-Gly-Asp-Ser) is sufficient to promote the transition of VSMCs from the contractile to the synthetic phenotype. Therefore, we treated VSMCs with this fragment to promote the cells from the contractile to the synthetic phenotype.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Fukuda

Satoh

et al. 2000

ATVB

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Abstract-We previously demonstrated that homogeneous cultures of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats produce angiotensin II (Ang II) in response to increases in the levels of angiotensinogen, cathepsin D, and angiotensin-converting enzyme (ACE). The change of VSMCs from the contractile to the synthetic phenotype increased the amount of synthetic organelles, resulting in the production of proteases and growth factors. To evaluate the contribution of the synthetic phenotype to the generation of Ang II, we examined the effect of fibronectin (FN), which reportedly induces the synthetic phenotype, on the Ang II-generating system in VSMCs. Cultured VSMCs from Wistar-Kyoto rats were incubated with an active fragment of FN, Arg-Gly-Asp-Ser, for 24, 48, or 72 hours after synchronization of the cell cycle with 0.2% calf serum for 48 hours. Immunofluorescence and protein levels of ␣-smooth muscle (SM) actin and expression of SM22␣ mRNA, apparent in the contractile phenotype, were suppressed by FN, whereas expression of matrix Gla mRNA and osteopontin mRNA and protein, apparent in the synthetic phenotype, was increased. FN (1 to 1000 g/mL) dose-dependently increased DNA synthesis in the VSMCs, which was inhibited by the Ang II type 1 receptor antagonist CV-11974. Ang II-like immunoreactivity as determined by radioimmunoassay was significantly increased in conditioned medium from the VSMCs. In addition, mRNA for the Ang II-generating proteases cathepsin D and ACE was increased by FN. Expression of transforming growth factor-␤1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNAs was also increased by FN. These results indicate that the changes accompanying the alteration to the synthetic phenotype in homogeneous cultures of VSMCs increase expression of proteases such as cathepsin D and ACE, which then produce Ang II, and that these changes increase expression of growth factors that then induce growth of VSMCs.

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“…These processes were all distinctly slowed down by antibodies against the /3, integrin subunit (this antibody interfered with the attachment of the cells to fibronectin but not to vitronectin, another adhesive plasma protein that contains an RGD sequence). 122 The fibronectin receptors of the smooth muscle cells were isolated by sequential chromatography on columns of wheat germ agglutinin (WGA) and the cell-binding domain of fibronectin. 123 They were composed of two proteins with electrophoretic mobilities in sodium dodecyl sulfate (SDS)-polyacrylamide gels of 160 and 115 kDa under nonreducing conditions and of 150 and 130 kDa under reducing conditions.…”

mentioning

confidence: 99%

“…145146 This molecule contains an RGD sequence but binds to a cell surface receptor distinct from the fibronectin receptor, 147 and supports attachment and spreading of freshly isolated smooth muscle cells less efficiently than fibronectin. 122 Thrombospondin is a 450 kDa trimeric glycoprotein stored in platelet a-granules and released during platelet degranulation. It is synthesized by a number of normal and transformed cells in culture and shows binding affinities for a variety of plasma and extracellular matrix proteins.…”

mentioning

confidence: 99%

Regulation of differentiated properties and proliferation of arterial smooth muscle cells.

et al. 1990

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A substrate of the cell-attachment sequence of fibronectin (Arg-Gly-Asp-Ser) is sufficient to promote transition of arterial smooth muscle cells from a contractile to a synthetic phenotype

Cited by 98 publications

References 39 publications

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Regulation of differentiated properties and proliferation of arterial smooth muscle cells.

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