Expression of stem cell factor in human aortic endothelial and smooth muscle cells

Miyamoto, Tomofumi; Sasaguri, Yasuyuki; Sasaguri, Toshiyuki; S, Azakami; Yasukawa, Hideo; Kato, Seiya; Arima, Nobuyuki; Sugama, Kazushige; Morimatsu, Minoru

doi:10.1016/s0021-9150(96)06043-1

Cited by 59 publications

(45 citation statements)

References 31 publications

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“…SCF is mainly produced in the vasculature by endothelial cells and VSMCs (16,34,47), and its levels increase significantly in pathogenic stages (47). This ligand exists in both membranebound and soluble forms, and their production is regulated by alternative splicing mechanisms (27) or through the proteolytic action of MMP-9 (6, 16), which we and others (16) have also found to be upregulated in the fistula wall.…”

Section: Discussionmentioning

confidence: 67%

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Skartsis

Martinez

Duque

et al. 2014

American Journal of Physiology-Renal Physiology

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Skartsis N, Martinez L, Duque JC, Tabbara M, Velazquez OC, Asif A, Andreopoulos F, Salman LH, Vazquez-Padron RI. c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae. Am J Physiol Renal Physiol 307: F1095-F1104, 2014. First published September 3, 2014 doi:10.1152/ajprenal.00292.2014.-Stenosis of arteriovenous (A-V) fistulae secondary to neointimal hyperplasia (NIH) compromises dialysis delivery, which worsens patients' quality of life and increases medical costs associated with the maintenance of vascular accesses. In the present study, we evaluated the role of the receptor tyrosine kinase c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, whereas it was barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling, we analyzed the spatial and temporal pattern of c-Kit expression in the fistula wall. Interestingly, c-Kit immunoreactivity increased with time after anastomosis, which concurred with the accumulation of cells in the venous intima. In addition, c-Kit expression in A-V fistulae was positively altered by chronic kidney failure conditions. Both blockade of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor production with a specific short hairpin RNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Kit activity compromised the development of NIH in A-V fistulae created in c-Kit W/Wv mutant mice. These results suggest that targeting of the c-Kit signaling pathway may be an effective approach to prevent postoperative NIH in A-V fistulae. arteriovenous fistula; hemodialysis; neointima THE ARTERIOVENOUS (A-V) fistula is the preferred type of vascular access for hemodialysis patients (29). It achieves higher patency rates, has fewer complications than synthetic grafts (12,29,31), and has a lower risk of infections than central venous catheters (17,29). Despite its advantages, A-V fistulae frequently fail to mature or become dysfunctional after successful dialysis sessions, and this occurs primarily due to the development of neointimal hyperplasia (NIH) within the A-V fistula circuit (2, 5, 39). Stenosed A-V fistulae can sometimes be salvaged through angioplasty or surgical interventions, but these attempts often result in restenosis or additional complications (32). Therefore, there is an unmet medical need for treatments that prevent NIH and improve A-V fistula function. To this end, it is necessary to better define the factors underlying the pathological remodeling of the A-V fistula wall.A-V fistula maturation is a dynamic vascular process with multiple factors contributing to the development of NIH. These include vein configuration (22) In the present study, we investigated the role of c-Kit in the pathological remodeling of A-V fistulae. We show that activation of the c-Kit signaling pathway in adventitial and neointimal cells precedes arteri...

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Section: Discussionmentioning

confidence: 67%

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Skartsis

Martinez

Duque

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Frangogiannis et al 23 reported an increase in the number of mast cells in areas of collagen deposition and proliferating cell nuclear antigen expression and concluded that mast cells played an important role in myocardial remodeling and fibrosis after myocardial ischemia. Miyamoto et al 24 observed that SCF mRNA was expressed in vitro and in vivo in human aortic endothelial and smooth muscle cells. This ability of endothelial and smooth muscle cells to interact with mast cells via SCF-c-kit receptor binding suggests that it plays a role in the metabolism of the arterial wall because SCF may be a most important factor influencing mast cell number, phenotype, and function in both health and disease.…”

Section: Discussionmentioning

confidence: 99%

Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis

et al. 2008

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“…Gastrointestinal smooth muscle cells also produce stem cell factor, the ligand for c-Kit (37,38). Stem cell factor is also synthesized by smooth muscle cells of the airway and the vasculature (18,28). In the airways, stem cell factor has been suggested to increase recruitment and promote survival of mast cells.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory gene expression by human colonic smooth muscle cells

Salinthone

Singer

Gerthoffer

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal mucosal cells and invading leukocytes produce inappropriate levels of cytokines and chemokines in human colitis. However, smooth muscle cells of the airway and vasculature also synthesize cytokines and chemokines. To determine whether human colonic myocytes can synthesize proinflammatory mediators, strips of circular smooth muscle and smooth muscle cells were isolated from human colon. Myocytes and muscle strips were stimulated with 10 ng/ml of IL-1β, TNF-α, and IFN-γ, respectively. Expression of mRNA for IL-1β, IL-6, IL-8, and cyclooxygenase-2 (COX-2) was induced within 2 h and continued to increase for 8–12 h. Regulated on activation, normal T cell-expressed and -secreted (RANTES) mRNA expression was slower, appearing at 8 h and increasing linearly through 20 h. Expression of all five mRNAs was inhibited by 0.1 μM MG-132, a proteosome inhibitor that blocks NF-κB activation. Expression of IL-1β, IL-6, IL-8, and COX-2 mRNA was reduced by 30 μM PP1, an Src family tyrosine kinase inhibitor, and by 25 μM SB-203580, a p38 MAPK inhibitor. MAPK/extracellular regulated kinase-1 inhibitor PD-98059 (25 μM) was much less effective. In conclusion, human colonic smooth muscle cells can synthesize and secrete interleukins (IL-1β and IL-6) and chemokines (IL-8 and RANTES) and upregulate expression of COX-2. Regulation of cytokine, chemokine, and COX-2 mRNA depends on multiple signaling pathways, including Src-family kinases, extracellular regulated kinase, p38 MAPKs, and NF-κB. SB-203580 was a consistent, efficacious inhibitor of inflammatory gene expression, suggesting an important role of p38 MAPK in synthetic functions of human colonic smooth muscle.

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Expression of stem cell factor in human aortic endothelial and smooth muscle cells

Cited by 59 publications

References 31 publications

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis

Inflammatory gene expression by human colonic smooth muscle cells

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