Shear stress induction of the tissue factor gene.

Lin, Chia-Chen; Almus-Jacobs, Fanny; Chen, Hsuan Hsu; Parry, Graham; Mackman, Nigel; Shyy, John Y.‐J.; Chien, Shu

doi:10.1172/jci119219

Cited by 225 publications

(159 citation statements)

References 51 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…In earlier studies, Sp1 was viewed as a component of the basal transcriptional machinery. However, recent studies have shown that Sp1 transactivation activity is also subject to regulation by several different extracellular cues including oxidative and shear stress (58,59). Our results now implicate the Sp1 transcription factor as a component in the hyperosmotic stress response that leads to the stimulated expression of sgk.…”

Section: Discussionsupporting

confidence: 61%

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Bell¹,

Leong²,

Kim³

et al. 2000

Journal of Biological Chemistry

143

149

View full text Add to dashboard Cite

We have established that the serum-and glucocorticoid-inducible protein kinase (Sgk) is a new component of the hyperosmotic stress response. Treatment of NMuMg mammary epithelial cells with the organic osmolyte, sorbitol, caused the stable accumulation of Sgk transcripts and protein after an approximately 4-h lag. Transient transfection of a series of sgk-CAT reporter plasmids containing either 5 deletions or continuous 6-base pair substitutions identified a hyperosmotic stress-regulated element that is GC-rich and is necessary for the sorbitol stimulation of sgk gene promoter activity. Gel shift analysis identified four major DNAprotein complexes in the hyperosmotic stress-regulated element that, by competition with excess consensus wild type and mutant oligonucleotides and by antibody supershifts, contains the Sp1 transcription factor. Several lines of evidence suggest that the p38 MAPK signaling pathway mediates the hyperosmotic stress stimulation of sgk gene expression. Treatment with pharmacological inhibitors of p38 MAPK or with a dominant negative form of MKK3, an upstream regulator of p38 MAPK, significantly reduced or ablated the sorbitol induction of sgk promoter activity or protein production. Using an in vitro peptide transphosphorylation assay, sorbitol treatment activates either endogenous or exogenous Sgk that is localized to the cytoplasmic compartment. Thus, we propose that the stimulated expression of enzymatically active Sgk after sorbitol treatment is a newly defined component of the p38 MAPK-mediated response to hyperosmotic stress.

show abstract

Section: Discussionsupporting

confidence: 61%

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Bell¹,

Leong²,

Kim³

et al. 2000

Journal of Biological Chemistry

143

149

View full text Add to dashboard Cite

show abstract

“…induction of tissue factor by shear stress. 21 Added to severe wall damage, constriction functions to increase shear stress and initiate CFVs. Epinephrine exerts additional sheardependent and -independent actions on platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

et al. 2000

View full text Add to dashboard Cite

Background-Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of factor Xa and the coagulant initiator complex tissue factor/factor VIIa. Methods and Results-To study the effects of TFPI gene transfer on thrombus formation, balloon-injured porcine carotid arteries were treated locally with an adenovirus encoding human TFPI (Ad-TFPI) or control virus. Gene transfer of TFPI was confirmed by detection of human TFPI in the conditioned medium of porcine carotid arteries kept in culture after in vivo transduction. When carotid flow was measured with Doppler probe 5 days after surgery, cyclic flow variations (CFVs) developed in 7 of 8 control pigs after constriction of the injured carotid artery by 40%, and all control-treated arteries occluded after 70% constriction. In contrast, CFVs were observed in only 1 of 8 Ad-TFPI-treated pigs after 40% constriction, and only 3 of 8 occluded after constriction by 70% (Pϭ0.0027 and Pϭ0.007, respectively).

show abstract

“…Because flow rate determines both the pressure difference generated across the construct during perfusion and the shear stress on the surface of the modules, the maximum flow rate that can ultimately be achieved is limited by the maximum shear stress to which the ECs can be exposed [typically 5-50 dynes͞cm 2 (14), depending on the vessel from which the cells originate] before they are dislodged from the channel wall or exhibit an altered phenotype such as increased tissue factor expression (15). It is for this reason that cylindrical, instead of spherical, modules were selected during the initial design stages.…”

Section: Fig 1 Modular Construct Design and Fabrication (A)mentioning

confidence: 99%

Vascularized organoid engineered by modular assembly enables blood perfusion

McGuigan

Sefton

2006

Proc. Natl. Acad. Sci. U.S.A.

339

299

View full text Add to dashboard Cite

Tissue engineering is one approach to address the donor-organ shortage, but to attain clinically significant viable cell densities in thick tissues, laboratory-constructed tissues must have an internal vascular supply. We have adopted a biomimetic approach and assembled microscale modular components, consisting of submillimeter-sized collagen gel rods seeded with endothelial cells (ECs) into a (micro)vascularized tissue; in some prototypes the gel contained HepG2 cells to illustrate the possibilities. The EC-covered modules then were assembled into a larger tube and perfused with medium or whole blood. The interstitial spaces among the modules formed interconnected channels that enabled this perfusion. Viable cell densities were high, within an order of magnitude of cell densities within tissues, and the percolating nature of the flow through the construct was evident in microcomputed tomography and Doppler ultrasound measurements. Most importantly, the ECs retained their nonthrombogenic phenotype and delayed clotting times and inhibited the loss of platelets associated with perfusion of whole blood through the construct. Unlike the conventional scaffold and cell-seeding paradigm of other tissue-engineering approaches, this modular construct has the potential to be scalable, uniform, and perfusable with whole blood, circumventing the limitations of other approaches.collagen gel modules ͉ endothelial cells ͉ tissue engineering

show abstract

Shear stress induction of the tissue factor gene.

Cited by 225 publications

References 51 publications

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

Vascularized organoid engineered by modular assembly enables blood perfusion

Contact Info

Product

Resources

About