scholarly journals Novel treatment avenues for uterine leiomyoma: a new implication for endothelin?

2018 ◽  
Vol 132 (20) ◽  
pp. 2261-2267
Author(s):  
Kedra Wallace ◽  
Krystal Chatman ◽  
Venessia Johnson ◽  
Alexis Brookins ◽  
John Rushing ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Culture Media ◽  
Uterine Fibroids ◽  
Muscle Cells ◽  
Angiogenic Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eta Receptor ◽  
Eta Receptor Antagonist

Cysteine-rich angiogenic inducer 61 (CYR61), an angiogenic factor whose expression is decreased in fibroids. The aim of the present study was to determine if CYR61 secretion in smooth muscle cells (SMCs) is regulated by hypoxia and through the endothelin A (ETA) receptor. SMCs from fibroids (fSMC) and the adjacent myometrium smooth muscle cells (mSMCs) were extracted from ten women undergoing hysterectomy for uterine fibroids and cultured with or without 1.0 µM of an ETA receptor antagonist for 24 h under either normal or hypoxic oxygen conditions. Cellular secretion of endothelin-1 (ET-1) and CYR61 were measured via enzyme linked immunosorbent assay in the cell culture media. SMCs were collected to determine cell proliferation and CYR61 protein expression via Western blot. ET-1 secretion was significantly increased in fSMC and was decreased with blockade of the ETA receptor under both normoxia (P=0.0004) and hypoxia (P=0.008). CYR61 expression was decreased in fSMCs and significantly increased with blockade of the ETA receptor under hypoxia (P=0.04). Cell proliferation decreased with ETA blockade under normoxia (P=0.0001) and hypoxia (P=0.001). These results suggest that suppression of CYR61 secretion in fSMC is regulated by the ET-1 and that blockade with ETA could be considered for a future treatment option.

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

1990 ◽  
Vol 63 (02) ◽  
pp. 291-297 ◽  
Author(s):  
Herm-Jan M Brinkman ◽  
Marijke F van Buul-Worteiboer ◽  
Jan A van Mourik
Keyword(s):  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Muscle Cells ◽  
Smooth Muscle Cell Proliferation

SummaryWe observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A2 inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E2 (PGE2), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE2 was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE2 inhibits the serum-induced [3H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE2 and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells

2000 ◽  
Vol 279 (1) ◽  
pp. C248-C256 ◽  
Author(s):  
Liu Hua Wei ◽  
Aaron T. Jacobs ◽  
Sidney M. Morris ◽  
Louis J. Ignarro
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Protein Levels ◽  
Ifn Γ ◽  
Arginase Ii ◽  
Arginase I

The objectives of this study were to determine whether rat aortic smooth muscle cells (RASMC) express arginase and to elucidate the possible mechanisms involved in the regulation of arginase expression. The results show that RASMC contain basal arginase I (AI) activity, which is significantly enhanced by stimulating the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII) expression was not detected under any condition studied here. We further investigated the signal transduction pathways responsible for AI induction. AI mRNA and protein levels were enhanced by addition of forskolin (1 μM) and inhibited by H-89 (30 μM), suggesting positive regulation of AI by a protein kinase A pathway. Genistein (10 μg/ml) and sodium orthovanadate (Na3VO4; 10 μM) were used to investigate the role of tyrosine phosphorylation in the control of AI expression. Genistein inhibited, whereas Na3VO4enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-γ were investigated for their effects on AI induction. Dex (1 μM) and IFN-γ (100 U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI induction by IL-4 and IL-13. In combination, Dex and IFN-γ abolished AI induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased RASMC DNA synthesis as monitored by [3H]thymidine incorporation, demonstrating that upregulation of AI is correlated with an increase in cell proliferation. Blockade of AI induction by IFN-γ, H-89, or genistein also blocked the increase in cell proliferation. These observations are consistent with the possibility that upregulation of AI might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

scholarly journals EXPRESS: Ubiquitin‑specific protease 7 mediates platelet derived growth factor-induced pulmonary arterial smooth muscle cells proliferation

2021 ◽  
pp. 204589402110461
Author(s):  
Yanting Zhu ◽  
Qianqian Zhang ◽  
Xin Yan ◽  
Lu Liu ◽  
Cui Zhai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Specific Protease ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

Pulmonary arterial hypertension (PAH) is a devastating pulmonary vascular disease, in which the pathogenesis is complicated and unclear. Pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathological feature of PAH. It has been shown that ubiquitin-specific protease 7 (USP7) is involved in cancer cell proliferation via deubiquitinating and stabilizing E3 ubiquitin ligase mouse double minute 2 (MDM2). However, the effect of USP7 and MDM2 on platelet derived growth factor (PDGF) -induced PASMCs proliferation is uncertain. This study aims to explore this issue. Our results indicated that PDGF up-regulated USP7 protein expression and stimulated PASMCs proliferation; this was accompanied with the increase of MDM2, forkhead box O4 (FoxO4) reduction and elevation of CyclinD1. While prior transfection of USP7 siRNA blocked PDGF-induced MDM2 up-regulation, FoxO4 down-regulation, increase of CyclinD1 and cell proliferation. Pre-depletion of MDM2 by siRNA transfection reversed PDGF-induced reduction of FoxO4, up-regulation of CyclinD1 and PASMCs proliferation. Furthermore, pre-treatment of cells with proteasome inhibitor MG-132 also abolished PDGF-induced FoxO4 reduction, CyclinD1 elevation and cell proliferation. Our study suggests that USP7 up-regulates MDM2, which facilitates FoxO4 ubiquitinated degradation, and subsequently increases the expression of CyclinD1 to mediate PDGF-induced PASMCs proliferation.

scholarly journals Progesterone-dependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: keratinocyte growth factor as a progestomedin.

1994 ◽  
Vol 125 (2) ◽  
pp. 393-401 ◽  
Author(s):  
T Koji ◽  
M Chedid ◽  
J S Rubin ◽  
O D Slayden ◽  
K G Csaky ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Stromal Cells ◽  
Cellular Localization ◽  
Keratinocyte Growth Factor ◽  
Muscle Cells ◽  
Northern Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ru 486

In vitro studies have shown that keratinocyte growth factor (KGF, also known as FGF-7) is secreted by fibroblasts and is mitogenic specifically for epithelial cells. Therefore, KGF may be an important paracrine mediator of epithelial cell proliferation in vivo. Because stromal cells are thought to influence glandular proliferation in the primate endometrium, we investigated the hormonal regulation and cellular localization of KGF mRNA expression in the rhesus monkey uterus. Tissues were obtained both from naturally cycling monkeys in the follicular and luteal phases of the cycle, and from spayed monkeys that were either untreated or treated with estradiol (E2) alone, E2 followed by progesterone (P), E2 plus P, or E2 plus P plus an antiprogestin (RU 486). Northern blot analysis of total RNA with 32P-labeled probes revealed that the level of KGF mRNA in the endometrium was 70-100-fold greater in the luteal phase or after P treatment than in untreated, E2-treated, or follicular phase animals. Northern analysis also showed that KGF mRNA was present in the myometrium but was unaffected by hormonal state. RU 486 treatment prevented the P-induced elevation of endometrial KGF mRNA. P-dependent elevation of endometrial KGF expression was confirmed by measurement of KGF protein in tissue extracts using a two-site enzyme-linked immunosorbent assay. In situ hybridization with nonradioactive digoxigenin-labeled cDNA probes revealed that the KGF mRNA signal, which was present only in stromal and smooth muscle cells, was substantially increased by P primarily in the stromal cells located in the basalis region. Smooth muscle cells in the myometrium and the walls of the spiral arteries also expressed KGF mRNA, but the degree of this expression did not differ with hormonal state. P treatment led to increased proliferation in the glandular epithelium of the basalis region and to extensive growth of the spiral arteries. We conclude that the P-dependent increase in endometrial KGF resulted from a dual action of P: (a) a P-dependent induction of KGF expression in stromal cells, especially those in the basalis (zones III and IV), and (b) a P-dependent increase in the number of KGF-positive vascular smooth muscle cells caused by the proliferation of the spiral arteries. KGF is one of the first examples in primates of a P-induced, stromally derived growth factor that might function as a progestomedin.

Effects of hypoxia on rat airway smooth muscle cell proliferation

2003 ◽  
Vol 94 (4) ◽  
pp. 1403-1409 ◽  
Author(s):  
A. Cogo ◽  
G. Napolitano ◽  
M. C. Michoud ◽  
D. Ramos Barbon ◽  
M. Ward ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Cell Growth ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cell ◽  
Gf 109203X

Although it is well known that hypoxemia induces pulmonary vasoconstriction and vascular remodeling, due to the proliferation of both vascular smooth muscle cells and fibroblasts, the effects of hypoxemia on airway smooth muscle cells are not well characterized. The present study was designed to assess the in vitro effects of hypoxia (1 or 3% O2) on rat airway smooth muscle cell growth and response to mitogens (PDGF and 5-HT). Cell growth was assessed by cell counting and cell cycle analysis. Compared with normoxia (21% O2), there was a 42.2% increase in the rate of proliferation of cells exposed to 3% O2 (72 h, P = 0.006), as well as an enhanced response to PDGF (13.9% increase; P = 0.023) and to 5-HT (17.2% increase; P = 0.039). Exposure to 1% O2 (72 h) decreased cell proliferation by 21.0% ( P = 0.017) and reduced the increase in cell proliferation induced by PGDF and 5-HT by 16.2 and 15.7%, respectively ( P = 0.019 and P = 0.011). A significant inhibition in hypoxia-induced cell proliferation was observed after the administration of bisindolylmaleimide GF-109203X (a specific PKC inhibitor) or downregulation of PKC with PMA. Pretreatment with GF-109203X decreased proliferation by 21.5% ( P = 0.004) and PMA by 31.5% ( P = 0.005). These results show that hypoxia induces airway smooth muscle cell proliferation, which is at least partially dependent on PKC activation. They suggest that hypoxia could contribute to airway remodeling in patients suffering from chronic, severe respiratory diseases.

scholarly journals Troglitazone and pioglitazone attenuate agonist-dependent Ca2+ mobilization and cell proliferation in vascular smooth muscle cells

1999 ◽  
Vol 128 (3) ◽  
pp. 673-683 ◽  
Author(s):  
Michiko Asano ◽  
Toshiaki Nakajima ◽  
Kuniaki Iwasawa ◽  
Toshihiro Morita ◽  
Fumitaka Nakamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

scholarly journals Relationship between spontaneous Ca2+ oscillations and cell proliferation in cultured longitudinal smooth muscle cells.

1993 ◽  
Vol 61 ◽  
pp. 119
Author(s):  
Megumi Kawanishi ◽  
Hisayuki Ohata ◽  
Kazutaka Momose ◽  
Chikako Uneyama ◽  
Michihito Takahashi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Longitudinal Smooth Muscle

scholarly journals Pressure promotes cell proliferation in rat cultured vascular smooth muscle cells.

1994 ◽  
Vol 64 ◽  
pp. 248
Author(s):  
Keiichi Hishikawa ◽  
Toshio Nakaki ◽  
Takeshi Marumo ◽  
Ryuichi Kato
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

Secretion of Brain Natriuretic Peptide in Cultured Human Coronary Vascular Smooth Muscle Cells

2000 ◽  
Vol 6 (S2) ◽  
pp. 598-599
Author(s):  
J. Lin ◽  
C. Wei
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Tone ◽  
Culture Media ◽  
Muscle Cells ◽  
Ventricular Myocardium

Brain natriuretic peptide (BNP) is a peptide of cardiac origin which regulates plasma volume as well as vascular tone and growth. Recently, we have reported that brain natriuretic peptide is a potent inhibitor of endothelin-1-mediated proliferation in human coronary vascular smooth muscle cells (HCoVSMC). While brain natriuretic peptide has been reported to be produced and released from atrial and ventricular myocardium, we hypothesize that brain natriuretic peptide may be present and secreted from human coronary vascular smooth muscle cells.Therefore, the present study was designed to investigate the secretion of brain natriuretic peptide in cultured human coronary vascular smooth muscle cells (HCoVSMC: Clonetics, San Diego, CA). The concentration of brain natriuretic peptide, and its second messenger cGMP, in culture media (48 hours) was determined by radioimmunoassay (Phoenix, Mountain View, CA). The presence of brain natriuretic peptide was determined by immunohistochemical staining using a human brain natriuretic peptide polyclonal antibody.

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