Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells

Ozasa, Yukako; Akazawa, Hiroshi; Qin, Yingjie; Tateno, Kaoru; Ito, Kei; Kudo-Sakamoto, Yoko; Yano, Masamichi; Yabumoto, Chizuru; Naito, Atsuhiko T.; Oka, Tôru; Lee, Jong-Kook; Minamino, Tohru; Nagai, Toshio; Kobayashi, Yoshio; Komuro, Issei

doi:10.1038/hr.2013.52

Cited by 38 publications

(30 citation statements)

References 32 publications

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“…These findings are consistent with a previous report showing that Ang-II activates the Notch pathway through g-secretase dependent cleavage in HEK293 cells ectopically expressing the Ang-II type 1 receptor [17]. We tested the relevance of these findings in vivo by generating a mouse model in which the g-secretase complex is genetically targeted through the inducible ubiquitous elimination of Psen1/Psen2 genes in adults.…”

Section: Discussionsupporting

confidence: 89%

“…This protective outcome suggests that GSIs are a possible treatment for hypertension. Previously, Ozasa et al [17] demonstrated that systemic GSI The g-secretase complex is needed to maintain Ang-II-induced hypertension and left ventricular hypertrophy. Psen1 f/f ;Psen2 À/À ;Cre ERT2/ERT2 mice were treated with vehicle or 4-OHT as indicated.…”

Section: Discussionmentioning

confidence: 99%

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Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Rivera‐Torres

Guzmán‐Martínez

Villa‐Bellosta

et al. 2015

Journal of Hypertension

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The Notch pathway is activated in the vasculature of mice with hypertension and LVH, and its inhibition via inducible genetic γ-secretase deletion protects against both conditions. Preliminary observations in hypertensive patients with LVH support the translational potential of these findings. Moreover, GSI treatment protects wild-type mice from Ang-II-induced LVH without affecting blood pressure. Our results unveil the potential use of GSIs in the treatment of hypertensive patients with LVH.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Rivera‐Torres

Guzmán‐Martínez

Villa‐Bellosta

et al. 2015

Journal of Hypertension

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“…VSMC proliferation has an important role in hypertension pathogenesis 27 and vascular remodeling in atherosclerosis. 28,29 In the hypertensive state, the D 1 -like receptor-mediated natriureis is impaired due to receptor hyperphosphorylation, 30 which leads to its uncoupling from the G protein. As a major mitogenic factor, NPY has been shown to stimulate the proliferation of VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells

et al. 2015

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Proliferation of vascular smooth muscle cells (VSMCs) is thought to have a key role in the development of atherosclerotic lesions. Neuropeptide Y (NPY), norepinephrine and dopamine are sympathetic neurotransmitters. NPY has been particularly shown to stimulate proliferation of VSMCs. NPY, norepinephrine and dopamine are all sympathetic transmitters. In our previous study, we found that in the presence of the dopamine receptor, the α1-adrenergic receptor-mediated VSMC proliferation is reduced. We hypothesize that the activation of the D1-like receptor might inhibit the NPY-mediated VSMC proliferation. In our present study, we found that NPY, mainly via the Y1 receptor, increased VSMC proliferation. This was determined by [(3)H]-thymidine incorporation, in a concentration (10(-11) to 10(-8) M)-dependent manner. In the presence of the D1-like receptor agonist, fenoldopam (10(-12) to 10(-5) M), the stimulatory effect of NPY on VSMC proliferation was reduced. The involvement of the D1-like receptor was confirmed when the inhibitory effect of fenoldopam was reversed in the presence of the D1-like receptor antagonist SCH-23390 (10(-8) M). Moreover, the inhibitory effect of fenoldopam on NPY-mediated VSMC proliferation was also blocked in the presence of the PKA inhibitor 14-22 (10(-6) M). Protein kinase A activator 8-(4-chlorophenylthio) adenosine-3,5-cyclic monophosphorothioate, Sp-isomer sodium salt (10(-6) M) could simulate the stimulatory effect of fenoldopam. It indicated that the inhibitory effect of D1-like receptors on NPY-mediated VSMC proliferation may have an important role in the regulation of blood pressure or prevention of atherosclerosis.

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“…Down-regulation of Notch 1 reduced the growth and invasion of prostate cancer cells [42]. Notch activation promoted the migration and proliferation in vascular smooth muscle cells [43]. It has been reported that overexpression of CLDN-1 activates the Notch signaling pathway by up-regulating MMP and ERK1/2 [44,45].…”

Section: Discussionmentioning

confidence: 98%

CLDN-1 promoted the epithelial to migration and mesenchymal transition (EMT) in human bronchial epithelial cells via Notch pathway

Sun

Mai

et al. 2017

Mol Cell Biochem

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Claudin-1 (CLDN-1) is one of main tight junction components that play an important role in epithelial-mesenchymal transition (EMT). However, the effects of CLDN-1 on the migration and EMT induced by TGF-β1 in primary normal human bronchial epithelial (NHBE) and BEAS-2B cells have not been clear. The expression of CLDN-1 was quantified by Western blotting in NHBE and BEAS-2B cells. Cell migration and invasion were detected using transwell assays. The expression level of E-cadherin, N-cadherin, α-SMA, and Vimentin was evaluated by quantitative real-time PCR and Western blotting. Here we showed that the protein expression of CLDN-1 was increased exposed to TGF-β1 in a dose- and time-dependent manner. Knockdown of CLDN-1 using small interfering CLDN-1 RNA (siCLDN-1) prevented the migration and invasion in NHBE and BEAS-2B cells. Moreover, depletion of CLDN-1 promoted the E-cadherin expression and decreased the mRNA and protein levels of N-cadherin, α-SMA, and Vimentin induced by TGF-β1. Furthermore, CLDN-1 silencing resulted in the reduction of the Notch intracellular domain (NICD) and hairy enhancer of split-1 (Hes-1) in mRNA and protein level. Jagged-1, an activator of Notch signaling pathway, abrogated the protective function of siCLDN-1 in migration and EMT. In conclusion, CLDN-1 promoted the migration and EMT through the Notch signaling pathway.

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Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells

Cited by 38 publications

References 32 publications

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells

CLDN-1 promoted the epithelial to migration and mesenchymal transition (EMT) in human bronchial epithelial cells via Notch pathway

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