Morphogenic Effects of Endothelin-1 on Vascular Smooth Muscle Cells

Hahn, Alfred W.A.; Regenass, Stefan; Resink, Thérèse J.; Kern, Frances; Bühler, Fritz R.

doi:10.1159/000158994

Cited by 17 publications

(5 citation statements)

References 22 publications

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“…After ET-1 activates its receptor, it primarily causes VSMC proliferation through activation of the MAPK signal transduction pathway [55]. Hahn et al [56] showed that ET-1 disturbed G 1 anaphase and S prophase in the cell cycle. Furthermore, the early response genes c-fos and c-myc are intranuclear oncogenes, which play a critical role in cell information transfer.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we observed that the activity of MMP-2 was inhibited by AP-1 siRNA. Given the diversity, however, the promoters of MMPs exhibit a high degree of similarity in their cisacting regulatory elements, which include the AP-1 site located between -65 and -79 bp in all the promoters, with the exception of MMP-2 (gelatinase A) [56]. The promoter of MMP-2 (gelatinase A) is notably distinct from other MMP family members.…”

Section: Discussionmentioning

confidence: 99%

“…The promoter of MMP-2 (gelatinase A) is notably distinct from other MMP family members. Not only does it lack the adjacent AP-1 and PEA3 elements but it is also missing the classical TATA binding site [56]. Moreover, previous studies have shown that the DNA sequence of the 5'-flanking region of the MMP-2 gene contains a series of cis-acting elements, including SP-1 AP-1 and r-IRE sites and the molecular weight fraction of transcription factors induced by cytokine [55].…”

Section: Discussionmentioning

confidence: 99%

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Toxicological Insight from AP-1 Silencing Study on Proliferation, Migration, and Dedifferentiation of Rat Vascular Smooth Muscle Cell

Zhang

Shen

et al. 2011

Cardiovasc Toxicol

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There has an effective way to prevent intimal hyperplasia on vascular smooth muscle cell (VSMC) proliferation in grafted veins. The activator protein-1 (AP-1) transcription factor plays an important role in cardiovascular generation and angioplasty. Once activated, AP-1 binds its specific DNA sequence to promote the proliferation of VSMC, differentiation, and migration. The objectives of this study were to determine toxicological effects of AP-1 silencing study on proliferation, migration, and dedifferentiation of rat vascular smooth muscle cell. To suppress the expression of AP-1 gene, AP-1 siRNA was used to interfere post-transcription in rat primary VSMCs. To observe the expression of SM α-actin and downstream genes of AP-1, the activity of cell matrix metal proteinases and the migration ability of VSMC was examined by a modified Boyden chamber assay. Effects of AP-1 siRNA on proliferation and differentiation in rat VSMCs were evaluated by cell cycle analysis, DNA synthesis, MTT-test, and immunofluorescence. The results showed that the level of SM α-actin protein expression was increased. AP-1 siRNA also significantly decreased the MTT extinction value, DNA synthesis, PCNA expression, and the cell migration velocity when compared to the control group. AP-1 siRNA also clearly arrested cell cycle of VSM at the G0/G1 phase. Zymographic and Western blotting analyses showed that AP-1 siRNA suppressed serum-induced MMP-2 expression. These data suggest that the AP-1 siRNA was able to effectively inhibit the proliferation, migration, and dedifferentiation of smooth muscle cells. Thus, AP-1 siRNA provides a novel method to prevent intimal hyperplasia in blood vessel angioplasty.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Toxicological Insight from AP-1 Silencing Study on Proliferation, Migration, and Dedifferentiation of Rat Vascular Smooth Muscle Cell

Zhang

Shen

et al. 2011

Cardiovasc Toxicol

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“…52 Although the vasoregulatory functions of the endothelins have been emphasized, reports emphasizing growth regulatory and other effects also are noteworthy. [53][54][55][56][57][58] Additionally, production of ET-1-deficient and ET A and ET B receptor-deficient mice indicate that the endothelins are important regulators of mammalian neural crest development. [59][60][61][62] The production of ET-1 is regulated, at least in part, at the level of preproendothelin-1 messenger RNA (mRNA) transcription.…”

Section: Endothelinmentioning

confidence: 99%

Hepatic Blood Flow Regulation by Stellate Cells in Normal and Injured Liver

Rockey¹

2001

Semin Liver Dis

200

135

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Hepatic stellate cells have received considerable attention as key components of the fibrogenic response to injury. Beyond this feature, they also have been implicated as regulators of sinusoidal vascular tone, and in disease states, in the pathogenesis of intrahepatic portal hypertension. The basis for this latter concept is derived from the following: (a) stellate cells are situated in a perisinusoidal orientation within the sinusoid, optimized for sinusoidal constriction; (b) a series of studies performed over the past decade have demonstrated that perisinusoidal stellate cells exhibit a remarkable capacity for cellular contraction, a characteristic that is most prominent after liver injury and stellate cell activation; and (c) in vivo microscopy studies have revealed that stellate cells can mediate sinusoidal constriction. Available evidence indicates that liver injury leads to a vascular disorder in which endothelin-1 is overproduced by stellate cells and endothelial cell-derived nitric oxide production is reduced. These abnormalities, in the context of exaggerated stellate cell contractility after liver injury, set up a paradigm in which stellate cells contribute to the increased intrahepatic resistance typical of portal hypertension. Furthermore, because stellate cell contractility and the mediators that control this function are dynamic processes, strategies that target exaggerated contractility provide an opportunity for novel therapeutics in intrahepatic portal hypertension.

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“…These characteristics suggest a morphogenic potential for ET-1. 32 Besides regulating vascular tone and vascular remodeling, ET-1 inhibits serum deprivation and nitric oxide-induced apoptosis. 33 Thus, the observations of ApoJ-exposed VSMCs in this study may, in part, be explained by ET-1 action.…”

mentioning

confidence: 99%