Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells

Eto, Yoko; Nitta, Kosaku; Uchida, Keiko; Tsutsui, Takaaki; Natori, Kyoko; Kawashima, Akira; Yumura, Wako; Nihei, Hiroshi

doi:10.1016/s0024-3205(97)00018-0

Cited by 12 publications

(9 citation statements)

References 10 publications

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“…However, aHSCs incubated with PDGF-BB and 5-HT simultaneously displayed an elevated level of proliferation when compared with cells incubated with PDGF-BB alone. A similar observation was made by Eto et al, 44 who demonstrated the cumulative effects of 5-HT and PDGF-BB incubation on 5-HT 2A receptor expressing mesangial cells when compared with the effects of 5-HT or PDGF-BB alone. 5-HT 2B receptors have also been shown to interact with the signaling cascade associated with the PDGF receptor resulting in cell cycle progression via ERK1/2.…”

Section: Discussionsupporting

confidence: 82%

“…Moreover, the degree of apoptosis induced by spiperone was found to be equivalent to that induced by gliotoxin, which has been used to promote HSC apoptosis in vivo and enhance recovery from fibrosis in rats. 8 Whereas the ability of various 5-HT receptors to regulate proliferation is well documented, 31,32,44 their function as regulators of apoptosis, by contrast, is less well established. Studies by Choi et al 53 demonstrate a role for the 5-HT 2B receptor in mouse embryogenesis, with antagonism of the receptor at key stages of development causing apoptosis and abnormal sarcomeric organization in the cephalic region, heart, and neural tube.…”

Section: Discussionmentioning

confidence: 99%

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A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis

Ruddell

Oakley

Hussain

et al. 2006

The American Journal of Pathology

173

149

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The hepatic stellate cell (HSC) is recognized as one of the key mediators in the progression of hepatic fibrosis.1-3 In the normal healthy liver, HSCs function to regulate sinusoidal blood flow and the traffic of macromolecules across the space of Disse and also act as a store for vitamin A. In response to hepatic injury, HSCs undergo a gross morphological change in terms of both function and phenotype in a process termed "activation", transforming to that of myofibroblast-like cell.1-3 The myofibroblast-like activated HSC (aHSC) is characterized by the expression of smooth muscle ␣-actin (␣-SMA), enhanced collagen production, expression of the tissue inhibitor of metalloproteinases-1, and the loss of vitamin A stores. Additionally, on activation, the normally quiescent HSC enters the cell cycle and, in response to both autocrine and paracrine stimulators, proliferates to produce a population of profibrogenic cells in the injured liver. Because the aHSC phenotype is relatively resistant to apoptosis due in part to the antiapoptotic effects of tissue inhibitor of metalloproteinases-1 and their high basal nuclear factor-B activity, 4,5 there is a propensity in the chronically injured liver for aHSCs to persist and perpetuate. This leads to the excess deposition of cross-linked collagen resulting in both qualitative and quantitative modification of the hepatic extracellular matrix (ECM).6 If this process of ECM remodeling continues, then the liver becomes fibrotic, and cirrhosis eventually develops, accompanied by life threatening disturbance of normal liver physiology. There is currently much interest in improving our understanding of how HSC proliferation and apoptosis are regulated because in vivo experimental manipulation of these processes is known to attenuate the fibrogenic process. 5,[7][8][9] In particular, there is a drive to discover novel surface receptors on aHSCs that are able to attenuate proliferation and/or apoptosis in response to specific ligands.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis

Ruddell

Oakley

Hussain

et al. 2006

The American Journal of Pathology

173

149

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“…It is reported that 5-HT and sarpogrelate concentrations of 1 and 1 -10 μM, respectively, were used in experiments to determine inhibition of rat aortic smooth muscle proliferation (24), IL-6 production in human aortic smooth muscle (25), inhibition of the rat mesangial cells proliferation (26) and human platelet aggregation (27). The concentrations of 5-HT and sarpogrelate in the above experiments were similar to those of VCAM-1 expression in HUVECs.…”

Section: Cell Culture and Experimental Protocol In Vitromentioning

confidence: 82%

Serotonin Potentiates High-Glucose^|^ndash;Induced Endothelial Injury: the Role of Serotonin and 5-HT2A Receptors in Promoting Thrombosis in Diabetes

Yamada¹,

Niki²,

Nagai³

et al. 2012

J Pharmacol Sci

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Abstract. To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT 2A receptor antagonist, on thrombus formation in diabetic rats. In streptozotocin-induced diabetic rats, polyethylene tubeinduced thrombus formation was enhanced compared with that in normal rats. The thrombogenesis was inhibited by sarpogrelate; cilostazol, a PDE3 inhibitor; and aspirin, a COX inhibitor, by 75.8%, 42.3%, and 34.3%, respectively. The inhibition by sarpogrelate was more pronounced in diabetic rats than normal ones. High glucose and 5-HT increased the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and combination of both high glucose and 5-HT further potentiated the effect. Sarpogrelate but not aspirin inhibited the increase in VCAM-1 expression induced by high glucose and 5-HT. These findings suggest that 5-HT mediates the enhanced thrombogenesis in diabetes and suggests that a 5-HT 2A receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications.

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“…5HT has various receptor subtypes [2] that mediate both vasoconstriction and vasodilation [3], enhance mesangial cell proliferation [4] and promote platelet aggregation. Serum serotonin concentrations are elevated in diabetics [5], and there is evidence that the pathogenesis of diabetic nephropathy involves the 5-HT receptor subtype 2A receptor (5-HT2A) on mesangial cells [4,6]. Sarpogrelate hydrochloride is a selective 5-HT2A antagonist and is clinically used for the treatment of cutaneous ulcers and ischemic changes associated with atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy

et al. 2008

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Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells

Cited by 12 publications

References 10 publications

A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis

A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis

Serotonin Potentiates High-Glucose^|^ndash;Induced Endothelial Injury: the Role of Serotonin and 5-HT2A Receptors in Promoting Thrombosis in Diabetes

Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy

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