Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling

Abstract

Aim: To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs). Methods: VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting. Results: Pretreatment with platonin (1-5 μmol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G 2 /M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation. Conclusion: Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G 2 /M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.

Piperine Inhibits Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration in Vascular Smooth Muscle Cells

“…8,27 In VSMCs, these responses are initiated when PDGF-BB induces the activation of downstream signaling molecules, such as by phosphorylation of ERK1/2 and p38. 7 Our data show that piperine reduces the phosphorylation of ERK1/2 in PDGF-BB-stimulated VSMCs in a dose-dependent manner and upregulates p27 kip1 expression.…”

“…6,7 Recently, studies have reported that PDGF-BB contributes to intracellular signaling through mitogen-activated protein kinases (MAPKs) in various cells. 8,9 VSMC migration and proliferation are also influenced by activated MAPKs, such as extracellular signalregulated kinase (ERK)1/2 and p38 MAPK. 10,11 Moreover, ROS are involved in the proliferation and migration of PDGF-BB-stimulated VSMCs.…”

Imatinib ameliorates renal morphological changes in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

“…Specifically, tyrosine-phosphorylated PDGF receptors interact with several other cytoplasmic proteins that constitute Src homology 2 domains, including phospholipase C␥, ras guanine 5=-triphosphatase-activating protein, phosphatidyl-inositol 3-kinase, and tyrosine phosphatase SHP-2 (5). These signaling molecules mediate cellular activities, including proliferation, migration, and differentiation in response to PDGF (5). Furthermore, PDGF transmits its signals to the intracellular space through activation of AKT and MAPKs (5).…”

“…These signaling molecules mediate cellular activities, including proliferation, migration, and differentiation in response to PDGF (5). Furthermore, PDGF transmits its signals to the intracellular space through activation of AKT and MAPKs (5). MAPKs phosphorylate JNKs, which in turn results in the phosphorylation of many transcription factors, including the c-Jun component of the activator protein-1 transcription family (5).…”

“…Furthermore, PDGF transmits its signals to the intracellular space through activation of AKT and MAPKs (5). MAPKs phosphorylate JNKs, which in turn results in the phosphorylation of many transcription factors, including the c-Jun component of the activator protein-1 transcription family (5). C-Jun is known to be required for PDGF-induced VSMC migration and proliferation, and JNK knockdown can attenuate cell migration and proliferation in PDGF-stimulated VSMCs (5).…”