PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway

Kim, Yun Hak; Lee, Seung Jin; Seo, Kyo Won; Bae, Jin Ung; Park, So Youn; Kim, Eun Kyoung; Bae, Sun Sik; Kim, Jae Ho; Kim, Chi Dae

doi:10.1194/jlr.m037176

Cited by 20 publications

(13 citation statements)

References 33 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 Other cytokines, including platelet-activating factor and IL-1b, have been implicated in MMP-2 expression in rat aortic smooth muscle cell via ERK activation. 35,36 Additionally, through ERK phosphorylation, Ang II also induces the expression of platelet-derived growth factor B-chain in rat ASMCs. 37 p38 MAPK and JNK do not appear to be involved in Ang II-induced MMP-2 upregulation in HASMCs (data not shown) because Ang II does not induce p38 MAPK and JNK phosphorylation (Figure 4a and c).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2

Wang

Qian

Sun

et al. 2015

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Increased levels of angiotensin II (Ang II) and activated matrix metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human ASMCs) have recently been implicated in the pathogenesis of thoracic aortic aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA development in Marfan Syndrome. However, there is scant data regarding the relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we investigated the effect of Ang II on MMP-2 expression in human ASMCs and used Western blotting to identify the Ang II receptors and intracellular signaling pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence data demonstrated that Ang II receptors were expressed on human ASMCs. Additionally, Ang II increased the expression of Ang II type 2 receptor (AT2R) but not AT1R at both the transcriptional and translational levels. Furthermore, Western blotting showed that Ang II increased MMP-2 expression in human ASMCs in a dose-and time-dependent manner. This response was completely inhibited by the AT1R inhibitor candesartan but not by the AT2R blocker PD123319. In addition, Ang II-induced upregulation of MMP-2 was mediated by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In conclusion, these results indicate that Ang II can increase the expression of MMP-2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that antagonists of AT1R and ERK1/2 may be useful for treating TAAs.Keywords: Angiotensin II, renin angiotensin system, matrix metalloproteinase-2, extracellular signal-regulated kinase 1/2, human aortic smooth muscle cells 2015; 240: 1564-1571. Experimental Biology and Medicine

show abstract

Section: Discussionmentioning

confidence: 99%

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2

Wang

Qian

Sun

et al. 2015

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…These results indicated that the effects of TQ involved mitochondria-dependent apoptosis pathway.Vascular smooth muscle cell migration and secretion of various extracellular matrix (ECM) proteins (mainly MMP2 and MMP9) by macrophages also contribute to the vascular remodelling 27. Furthermore, the release of MMP2 and MMP9 promotes VSMC proliferation and migration 28,29. TQ decreased migration and invasion, as well as the expression of MMP9 and MMP2 in A549 cells and human glioblastoma cells 30,31.…”

mentioning

confidence: 99%

Thymoquinone suppresses platelet‐derived growth factor‐BB–induced vascular smooth muscle cell proliferation, migration and neointimal formation

Zhu

Xiang

Zhao

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are mainly responsible for vascular occlusion diseases, such as pulmonary arterial hypertension and restenosis. Our previous study demonstrated thymoquinone (TQ) attenuated monocrotaline‐induced pulmonary arterial hypertension. The aim of the present study is to systematically examine inhibitory effects of TQ on platelet‐derived growth factor‐BB (PDGF‐BB)–induced proliferation and migration of VSMCs in vitro and neointimal formation in vivo and elucidate the potential mechanisms. Vascular smooth muscle cells were isolated from the aorta in rats. Cell viability and proliferation were measured in VSMCs using the MTT assay. Cell migration was detected by wound healing assay and Transwell assay. Alpha‐smooth muscle actin (α‐SMA) and Ki‐67‐positive cells were examined by immunofluorescence staining. Reactive oxygen species (ROS) generation and apoptosis were measured by flow cytometry and terminal deoxyribonucleotide transferase–mediated dUTP nick end labelling (TUNEL) staining, respectively. Molecules including the mitochondria‐dependent apoptosis factors, matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), PTEN/AKT and mitogen‐activated protein kinases (MAPKs) were determined by Western blot. Neointimal formation was induced by ligation in male Sprague Dawley rats and evaluated by HE staining. Thymoquinone inhibited PDGF‐BB–induced VSMC proliferation and the increase in α‐SMA and Ki‐67‐positive cells. Thymoquinone also induced apoptosis via mitochondria‐dependent apoptosis pathway and p38MAPK. Thymoquinone blocked VSMC migration by inhibiting MMP2. Finally, TQ reversed neointimal formation induced by ligation in rats. Thus, TQ is a potential candidate for the prevention and treatment of occlusive vascular diseases.

show abstract

“…A number of ADAMs (disintegrin metalloproteinases) containing an MMP-like catalytic domain, such as ADAM-10, ADAM-15, and ADAM-17 are also expressed in vascular cells [ 75 ]. It was shown that agonist stimulation of platelet-activating factor receptor (PAFR) belonging to GPCR family enhanced MMP-2 production in rat aortic primary vascular SMCs via the activation of a β-arrestin-dependent ERK signaling pathway [ 76 ]. PAF-induced MMP-2 production was significantly attenuated by ERK inhibition using molecular and pharmacological inhibitors suggesting that ERK signaling pathway is important for PAF-induced MMP-2 production in vascular SMCs.…”

Section: Discussionmentioning

confidence: 99%

Alpha1a-Adrenoceptor Genetic Variant Triggers Vascular Smooth Muscle Cell Hyperproliferation and Agonist Induced Hypertrophy via EGFR Transactivation Pathway

et al. 2015

View full text Add to dashboard Cite

α1a Adrenergic receptors (α1aARs) are the predominant AR subtype in human vascular smooth muscle cells (SMCs). α1aARs in resistance vessels are crucial in the control of blood pressure, yet the impact of naturally occurring human α1aAR genetic variants in cardiovascular disorders remains poorly understood. To this end, we present novel findings demonstrating that 3D cultures of vascular SMCs expressing human α1aAR-247R (247R) genetic variant demonstrate significantly increased SMC contractility compared with cells expressing the α1aAR-WT (WT) receptor. Stable expression of 247R genetic variant also triggers MMP/EGFR-transactivation dependent serum- and agonist-independent (constitutive) hyperproliferation and agonist-dependent hypertrophy of SMCs. Agonist stimulation reduces contractility Using pathway-specific inhibitors we determined that the observed hyperproliferation of 247R-expressing cells is triggered via β-arrestin1/Src/MMP-2/EGFR/ERK-dependent mechanism. MMP-2-specific siRNA inhibited 247R-triggered hyperproliferation indicating MMP-2 involvement in 247R-triggered hyperproliferation in SMCs. β-arrestin1-specific shRNA also inhibited 247R-triggered hyperproliferation but did not affect hypertrophy in 247R-expressing SMCs, indicating that agonist-dependent hypertrophy is independent of β-arrestin1. Our data reveal that in different cardiovascular cells the same human receptor genetic variant can activate alternative modulators of the same signaling pathway. Thus, our findings in SMCs demonstrate that depending on the type of cells expressing the same receptor (or receptor variant), different target-specific inhibitors could be used to modulate aberrant hyperproliferative or hypertrophic pathways in order to restore normal phenotype.

show abstract

PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway

Cited by 20 publications

References 33 publications

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2

Thymoquinone suppresses platelet‐derived growth factor‐BB–induced vascular smooth muscle cell proliferation, migration and neointimal formation

Alpha1a-Adrenoceptor Genetic Variant Triggers Vascular Smooth Muscle Cell Hyperproliferation and Agonist Induced Hypertrophy via EGFR Transactivation Pathway

Contact Info

Product

Resources

About