Shear stress induces transforming growth factor[ndash ]beta release by arterial endothelial cells

Cucina, Alessandra; Sterpetti, Antonio V.; Borrelli, Valeria; Pagliei, Sabrina; Cavallaro, Antonino; ]Angelo, Luciana Santoro D[apos

doi:10.1067/msy.1998.83187

Cited by 28 publications

(35 citation statements)

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“…Several candidate molecules have been identified, such as TGF β [7,76], GDNF [36,78] and bFGF [69], which can up-regulate the barrier properties by increasing the resistance and decreasing the paracellular permeability in brain endothelial, cells. Several lines of evidence suggest that the enhancement of endothelial barrier properties by astrocytes/ACM and shear stress may be related to TGF-β1 [19,28,76,80]. For example, astrocyte regulation of endothelial cell function has been shown to be mediated in part by astrocyte-derived TGF-β1 and TGF-β1 was shown to be present in ACM collected from rat astrocytes [23,28,76].…”

Section: Discussionmentioning

confidence: 99%

“…For example, astrocyte regulation of endothelial cell function has been shown to be mediated in part by astrocyte-derived TGF-β1 and TGF-β1 was shown to be present in ACM collected from rat astrocytes [23,28,76]. In addition, TGF-β1 expression is shown to be increased when human umbilical vein and bovine aortic arterial endothelial cells are exposed to shear stress [19,80]. In our preliminary experiments, treatment of HBMEC with TGF-β1 at a physiological relevant concentration (1 ng/ml) exhibited an increased resistance of the HBMEC monolayer (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

et al. 2007

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The blood-brain barrier (BBB) is a structural and functional barrier that regulates the passage of molecules into and out of the brain to maintain the neural microenvironment. We have previously developed the in vitro BBB model with human brain microvascular endothelial cells (HBMEC). However, in vivo HBMEC are shown to interact with astrocytes and also exposed to shear stress through blood flow. In an attempt to develop the BBB model to mimic the in vivo condition we constructed the flow-based in vitro BBB model using HBMEC and human fetal astrocytes (HFA). We also examined the effect of astrocyte conditioned medium (ACM) in lieu of HFA to study the role of secreted factor(s) on the BBB properties. The tightness of HBMEC monolayer was assessed by the permeability of dextran and propidium iodide as well as by measuring the transendothelial electrical resistance (TEER). We showed that the HBMEC permeability was reduced and TEER was increased by non-contact, co-cultivation with HFA and ACM. The exposure of HBMEC to shear stress also exhibited decreased permeability. Moreover, HFA/ACM and shear flow exhibited additive effect of decreasing the permeability of HBMEC monolayer. In addition, we showed that the HBMEC expression of ZO-1 (tight junction protein) was increased by co-cultivation with ACM and in response to shear stress. These findings suggest that the non-contact co-cultivation with HFA helps maintain the barrier properties of HBMEC by secreting factor(s) into the medium. Our in vitro flow model system with the cells of human origin should be useful for studying the interactions between endothelial cells, glial cells, and secreted factor(s) as well as the role of shear stress in the barrier property of HBMEC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

et al. 2007

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“…Induction of IL-6 in response to different types of mechanical stresses has been reported in several cell types, such as vascular endothelial cells [41][42][43] [7] could induce the production of IL-6 in TM cells, we selected a cyclic stretch regimen of 5% elongation per second as an in vitro model. Although in vitro stretch systems cannot fully represent the actual in vivo conditions, we believe that a moderate amount (5%) of stretching models the mechanical forces to which TM cells are normally exposed better than, e.g., larger levels of stress that might activate responses associated with cell damage.…”

Section: Discussionmentioning

confidence: 99%

“…Induction of IL-6 in response to different types of mechanical stresses has been reported in several cell types, such as vascular endothelial cells [41][42][43], vascular smooth muscle cells [44], cardiac myocytes [45], lung fibroblasts [46], and chondrocytes [47]. To investigate whether mechanical stress associated with mild fluctuations in IOP similar to those that may occur in normal physiologic conditions [7] could induce the production of IL-6 in TM cells, we selected a cyclic stretch regimen of 5% elongation per second as an in vitro model.…”

Section: Discussionmentioning

confidence: 99%

Induction of IL-6 expression by mechanical stress in the trabecular meshwork

Liton

Luna

Bodman

et al. 2005

Biochemical and Biophysical Research Communications

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The trabecular meshwork (TM)/Schlemm's canal (SC) outflow pathway is the tissue responsible for maintaining normal levels of intraocular pressure. In the present study, we investigate the effects of mechanical stress on the expression of IL-6 in the TM meshwork, as well as the effects of this cytokine on outflow pathway function. Application of cyclic mechanical stress to human TM primary cultures resulted in a statistically significant increase in both secretion and transcription of IL-6, compared to nonstressed controls. Addition of TGF-β1, which has been reported to be upregulated in TM cells under mechanical stress, also induced a significant activation of both the transcription and secretion of IL-6. Moreover, anti-TGF-b1 antibodies partially blocked the stretch-induced IL-6 production. Injection of IL-6 into perfused porcine anterior segments resulted in a 30% increase in outflow facility, as well as increased permeability through SC cell monolayers. These results suggest a role for IL-6 in the homeostatic modulation of aqueous humor outflow resistance. KeywordsTrabecular meshwork; Interleukin-6; Mechanical stress; TGF-β1; glaucomaThe trabecular meshwork (TM)/Schlemm's canal (SC) outflow pathway system constitutes the main route by which the aqueous humor exits the anterior chamber of the eye [1]. Maintenance of appropriate levels of aqueous humor outflow resistance through this pathway is critical in sustaining normal levels of intraocular pressure (IOP) [2,3]. Although it has been hypothesized that the TM/SC outflow pathway may respond to transient changes in IOP by altering its resistance to aqueous humor [4][5][6], thereby maintaining normal IOP levels, there is little experimental evidence explaining such potential homeostatic mechanisms.As a result of cyclic fluctuations of IOP with each heartbeat, the conventional outflow pathway is subjected to continuous cycles of stretch and relaxation that might be involved in tissue homeostasis and, consequently, in IOP regulation [7]. It has been well described that changes in IOP exert dramatic effects on the morphology of the outflow pathway [8][9][10][11][12]. Increased IOP results in distention and stretching of the outflow pathway and its contained cells, while decreased IOP leads to relaxation of the tissue. It has also been demonstrated that mechanical stress can trigger certain responses in TM cells, including cytoskeletal changes, induction of gene expression, and activation of regulatory pathways [13][14][15][16][17][18][19][20][21] One of the reported responses to increased IOP in perfused human anterior segments observed by gene array analysis is an increase in interleukin-6 (IL-6) mRNA [16]. IL-6 is well known to increase the permeability of vascular endothelium through effects on the paracellular pathway, induction of matrix metalloproteinases (MMPs), and vesicular trafficking [22][23][24]. This array of effects mediated by IL-6 suggests that this cytokine could affect aqueous humor outflow resistance in the outflow pathway by increasing ...

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“…TGF-β 1 is a multifunctional regulator; its actions are dependent on species, cell phenotype, growth conditions, and interaction with other growth factors 24,25 . In atherosclerosis, with disrupted blood flow patterns, TGF-β 1 promotes lesion formation and vascular smooth muscle cell (VSMC) proliferation 26,27 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Stenting the Parent Artery on Aneurysm Filling and Gene Expression of Various Potential Factors Involved in Healing of Experimental Aneurysms

et al. 2006

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Intracranial stents are increasingly used in the endovascular treatment of aneurysms, but very little is known regarding their effect on the cellular and molecular evolution of aneurysms. Bilateral venous pouch lateral wall carotid aneurysms were created in 20 dogs. All dogs then underwent angiography and balloon-expandable stenting of one aneurysm four to six weeks later. Fifteen dogs underwent aneurysm harvesting at one day (n=3), four days (n=4), seven days (n=3), and 14 days (n=5) for mRNA expression analysis, using axial sections taken from the aneurysm neck and fundus for RT-PCR amplification of four cytokines or growth factors: TNF-a, TGF-b1, MCP-1, and PDGF-BB; two adhesion molecules: VCAM-1 and PECAM-1; five matrix modifying agents; MMP-2, 9, TIMPs 1, 3, 4, and two cellular markers: CD34 and a-SMA. Five other dogs, sacrificed at 12 weeks, were examined for extent of filling of the aneurysm neck with organized tissue and for neointima formation at the aneurysm ostium. Angiography was performed prior to sacrifice in all animals, and compared with initial studies. Eleven out of 20 stented aneurysms showed a favorable angiographic evolution, while none of the 20 non-stented aneurysms improved (p=0.001). Pathology showed partially occluded aneurysms, with neointima formation around the stent struts. Observed trends in mRNA expression, that stenting increased expression of genes involved in organization and neointima formation, agreed with experimental hypotheses, but differences between stented and non-stented aneurysms did not reach statistical significance. Parent vessel stenting was associated with angiographic improvement of aneurysm appearance. Modifications in mRNA expression patterns following stenting deserve further study to better establish potential molecular targets to promote aneurysm healing.

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Shear stress induces transforming growth factor[ndash ]beta release by arterial endothelial cells

Cited by 28 publications

References 0 publications

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

Induction of IL-6 expression by mechanical stress in the trabecular meshwork

Effects of Stenting the Parent Artery on Aneurysm Filling and Gene Expression of Various Potential Factors Involved in Healing of Experimental Aneurysms

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