scholarly journals Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 640
Author(s):  
Jeong Hee Lee ◽  
Seok Tae Choi ◽  
Young Jin Kang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Protein Levels ◽  
Phenotype Markers ◽  
Phenotype Switching ◽  
And Migration ◽  
Synthetic Phenotype

Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease.

scholarly journals Hypoxia-induced migration in pulmonary arterial smooth muscle cells requires calcium-dependent upregulation of aquaporin 1

2012 ◽  
Vol 303 (4) ◽  
pp. L343-L353 ◽  
Author(s):  
Kyle Leggett ◽  
Julie Maylor ◽  
Clark Undem ◽  
Ning Lai ◽  
Wenju Lu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Aquaporin 1 ◽  
Protein Levels ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
And Migration

Pulmonary arterial smooth muscle cell (PASMC) migration is a key component of the vascular remodeling that occurs during the development of hypoxic pulmonary hypertension, although the mechanisms governing this phenomenon remain poorly understood. Aquaporin-1 (AQP1), an integral membrane water channel protein, has recently been shown to aid in migration of endothelial cells. Since AQP1 is expressed in certain types of vascular smooth muscle, we hypothesized that AQP1 would be expressed in PASMCs and would be required for migration in response to hypoxia. Using PCR and immunoblot techniques, we determined the expression of AQPs in pulmonary vascular smooth muscle and the effect of hypoxia on AQP levels, and we examined the role of AQP1 in hypoxia-induced migration in rat PASMCs using Transwell filter assays. Moreover, since the cytoplasmic tail of AQP1 contains a putative calcium binding site and an increase in intracellular calcium concentration ([Ca2+]i) is a hallmark of hypoxic exposure in PASMCs, we also determined whether the responses were Ca2+ dependent. Results were compared with those obtained in aortic smooth muscle cells (AoSMCs). We found that although AQP1 was abundant in both PASMCs and AoSMCs, hypoxia selectively increased AQP1 protein levels, [Ca2+]i, and migration in PASMCs. Blockade of Ca2+ entry through voltage-dependent Ca2+ or nonselective cation channels prevented the hypoxia-induced increase in PASMC [Ca2+]i, AQP1 levels, and migration. Silencing AQP1 via siRNA also prevented hypoxia-induced migration of PASMCs. Our results suggest that hypoxia induces a PASMC-specific increase in [Ca2+]i that results in increased AQP1 protein levels and cell migration.

Role of cyclic AMP response element binding protein (CREB) in angiotensin II-induced responses in vascular smooth muscle cells

2020 ◽  
Author(s):  
Vanessa Truong ◽  
Madhu B Anand-Srivastava ◽  
Ashok K Srivastava
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Response Element ◽  
And Migration

Cyclic adenosine monophosphate response element (CRE) binding protein (CREB) is a nuclear transcription factor that regulates the transcription of several genes containing the CRE sites in their promoters. CREB is activated by phosphorylation on a key serine residue, Ser 311, in response to a wide variety of extracellular stimuli including angiotensin II (Ang II). Ang II is an important vasoactive peptide and mitogen for vascular smooth muscle cells (VSMC) that in addition to regulating the contractile response in VSMC also plays an important role in phenotypic switch of vascular smooth muscle cells (VSMC) from contractile to a synthetic state. The synthetic VSMC are known to exhibit proliferative and migratory properties due to hyperactivation of Ang II-induced signaling events. Ang II has been shown to induce CREB phosphorylation/activation and transcription of genes implicated in proliferation, growth and migration. Here, we have highlighted some key studies that have demonstrated an important role of CREB in Ang II-mediated gene transcription, proliferation, hypertrophy and migration of VSMC.

Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells

2002 ◽  
Vol 283 (1) ◽  
pp. H204-H212 ◽  
Author(s):  
Nobuya Fujita ◽  
Yusuke Furukawa ◽  
Naoki Itabashi ◽  
Koji Okada ◽  
Toshikazu Saito ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mrna Level ◽  
Muscle Cells ◽  
Ang Ii ◽  
Protein Levels ◽  
Biological Responses ◽  
Subunit Expression

E2F is a family of transcriptional factors that control G1/S transition. We investigated how the E2F family participates in the biological responses of vascular smooth muscle cells (VSMC) to vasoconstrictive hormones compared with fetal bovine serum (FBS). FBS induced upregulation of E2F-1 and E2F-5 at both mRNA and protein levels and slightly reduced E2F-3 protein. Angiotensin II (ANG II) and arginine vasopressin increased E2F-3 protein, but not E2F-1 and E2F-5, without upregulating its mRNA level. FBS transactivated the E2F-1 gene through the induction of free E2F-1 binding onto its promoter, whereas ANG II-induced binding of E2F-3 did not result in activation of the E2F-1 promoter. These changes are responsible for hypertrophic or hyperplastic response of VSMC to different growth factors or stimulants. In contrast, both FBS and vasoconstrictive hormones drove transcription of the cdc6 gene by downregulating p130 and recruiting free E2F-3 in the latter, which underlies the progression of VSMC into S phase.

scholarly journals Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Jie Su ◽  
Han-Ting Xu ◽  
Jing-Jing Yu ◽  
Jian-Li Gao ◽  
Jing Lei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Muscle Cells ◽  
Mapk Signaling ◽  
Ang Ii ◽  
And Migration ◽  
Proliferation And Migration

Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism.Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aortain vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level.Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.

Abstract 366: Nox1-Derived Superoxide Anion Mediates Stretch-induced Phenotypic Switching in Smooth Muscle Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Andres I Rodriguez ◽  
Patrick J Pagano
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Superoxide Production ◽  
Phenotypic Switching ◽  
Mrna Levels ◽  
Protein Levels ◽  
Synthetic Phenotype

Hemodynamic forces in the vessel wall have profound influences on function, structure and pathology of vascular cells. The predominant mechanical force influencing vascular smooth muscle cells (VSMC) structure and signaling is cyclic stretch (CS). Aberrant CS can direct VSMC to a synthetic phenotype (SP) characterized by increased VSMC migration, loss of contractility and matrix production. Some evidence suggests that CS is capable of inducing reactive oxygen species (ROS); however, the mechanisms by which stretch-derived ROS can induce a VSMC SP are poorly understood. Here we postulate that the NADPH oxidase isoform Nox1, which is an important source of ROS in vascular disease, is involved in a CS-mediated SP. In VSMC subjected to CS (10%, 1Hz) there was an increase in Nox1 mRNA levels (3.9 ± 0.14 fold of increase after 6 hr of CS), Nox1 protein levels (1.44 ± 0.04 fold increase after 24 hr CS) and Nox1-derived superoxide production (CS: 13.82±1.34 vs static: 6.61±0.67 pmol of superoxide/min/mg protein after 24 hr). Using our recently-developed specific peptide inhibitor of Nox1 (NoxA1ds), CS-induced superoxide production abated to baseline levels (6.61±0.67, 13.82±1.34 and 5.06±0.76 pmol of superoxide/min/mg protein; for static, CS and CS+NoxA1ds respectively). Furthermore, osteopontin protein levels, a VSMC SP marker, were increased by CS for 24 hrs (1.25±0.04 fold higher than static) and abolished by NoxA1ds pretreatment (0.96±0.19 fold of static). On the other hand, calponin protein levels, a VSMC contractile phenotype marker, were decreased by CS and restored by pretreatment with NoxA1ds (0.67±0.05- and 0.93±0.12-fold change from static respectively). Finally, we demonstrate that stretch-induced migration of smooth muscle cells is promoted by Nox1-derived superoxide (46.36±1.47, 56.16±1.74 and 40.98±2.46 % of scratch wound closure for static, CS and CS+NoxA1ds treatments respectively). These results suggest that Nox1-derived superoxide mediates a synthetic phenotype in vascular smooth muscle under CS, and identify Nox1 as a potential therapeutic target for the treatment of diseases such as atherosclerosis and hypertension which are characterized by VMSC SP.

Oxidative Stress Produced with Cell Migration Increases Synthetic Phenotype of Vascular Smooth Muscle Cells

2005 ◽  
Vol 33 (11) ◽  
pp. 1546-1554 ◽  
Author(s):  
Hak-Joon Sung ◽  
Suzanne G. Eskin ◽  
Yumiko Sakurai ◽  
Andrew Yee ◽  
Noriyuki Kataoka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Synthetic Phenotype

Angiotensin II modulates frizzled-2 receptor expression in rat vascular smooth muscle cells

2005 ◽  
Vol 108 (6) ◽  
pp. 523-530 ◽  
Author(s):  
Giovanna CASTOLDI ◽  
Serena REDAELLI ◽  
Willy M. M. van de GREEF ◽  
Cira R. T. di GIOIA ◽  
Giuseppe BUSCA ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Aortic Smooth Muscle

Ang II (angiotensin II) has multiple effects on vascular smooth muscle cells through the modulation of different classes of genes. Using the mRNA differential-display method to investigate gene expression in rat aortic smooth muscle cells in culture in response to 3 h of Ang II stimulation, we observed that Ang II down-regulated the expression of a member of the family of transmembrane receptors for Wnt proteins that was identified as Fzd2 [Fzd (frizzled)-2 receptor]. Fzds are a class of highly conserved genes playing a fundamental role in the developmental processes. In vitro, time course experiments demonstrated that Ang II induced a significant increase (P<0.05) in Fzd2 expression after 30 min, whereas it caused a significant decrease (P<0.05) in Fzd2 expression at 3 h. A similar rapid up-regulation after Ang II stimulation for 30 min was evident for TGFβ1 (transforming growth factor β1; P<0.05). To investigate whether Ang II also modulated Fzd2 expression in vivo, exogenous Ang II was administered to Sprague–Dawley rats (200 ng·kg−1 of body weight·min−1; subcutaneously) for 1 and 4 weeks. Control rats received normal saline. After treatment, systolic blood pressure was significantly higher (P<0.01), whereas plasma renin activity was suppressed (P<0.01) in Ang II- compared with the saline-treated rats. Ang II administration for 1 week did not modify Fzd2 expression in aorta of Ang II-treated rats, whereas Ang II administration for 4 weeks increased Fzd2 mRNA expression (P<0.05) in the tunica media of the aorta, resulting in a positive immunostaining for fibronectin at this time point. In conclusion, our data demonstrate that Ang II modulates Fzd2 expression in aortic smooth muscle cells both in vitro and in vivo.

RNAi-mediated Rab5a suppression inhibits proliferation and migration of vascular smooth muscle cells

2010 ◽  
Vol 65 (5) ◽  
pp. 507-514 ◽  
Author(s):  
Zhigang Ma ◽  
Hao Wang ◽  
Liang Wu ◽  
Lei Zhu ◽  
Weihao Shi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
And Migration ◽  
Proliferation And Migration
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