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https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#1
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#2
Hiroshi Kono, Hideki Fujii, Katsue Suzuki-Inoue, Osamu Inoue, Shinji Furuya, Kazuyoshi Hirayama, Yasuhiro Akazawa, Yuuki Nakata, Chao Sun, Nagaharu Tsukiji, Toshiaki Shirai, Yukio Ozaki
BACKGROUND AND AIM: The aim of the present study was to investigate the role of CLEC-2 in liver regeneration following partial liver resection in mice. MATERIALS AND METHODS: Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT), CLEC-2 deleted (KO), or CLEC-2 deleted specifically from platelets (flKO) mice were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin...
March 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28268217/a-phenanthrene-derivative-5-7-dimethoxy-1-4-phenanthrenequinone-inhibits-cell-adhesion-molecule-expression-and-migration-in-vascular-endothelial-and-smooth-muscle-cells
#3
Huey-Ming Lo, Tsong-Long Hwang, Wen-Bin Wu
The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs...
2017: Pharmacology
https://www.readbyqxmd.com/read/28266802/polydatin-inhibits-cell-proliferation-and-induces-apoptosis-in-laryngeal-cancer-and-hela-cells-via-suppression-of-the-pdgf-akt-signaling-pathway
#4
Haixia Li, Baoyuan Shi, Yanyun Li, Fengfang Yin
Polydatin (PD), a stilbene compound extracted from Polygonum cuspidatum, is suggested to possess anti-cancer activities, including inhibition of cell proliferation, cell cycle arrest, and induction of apoptosis. The platelet-derived growth factor (PDGF)/AKT signaling pathway plays complex roles in tumor suppression. However, the effect of PD on the PDGF/AKT signaling pathway in laryngeal cancer and HeLa cells has not been explored. MTT assay and flow cytometry showed that PD inhibited cell proliferation and induced apoptosis in Hep-2 and AMC-HN-8 cells...
March 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28260800/a-novel-stat3-inhibitor-negatively-modulates-platelet-activation-and-aggregation
#5
Zhuan Xu, Yu-Jia Xu, Ya-Nan Hao, Li-Jie Ren, Zu-Bin Zhang, Xin Xu, Bi-Yin Cao, Ke-Sheng Dai, Li Zhu, Qi Fang, Yan Kong, Xin-Liang Mao
The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively...
March 6, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28255363/exosomes-derived-from-human-platelet-rich-plasma-prevent-apoptosis-induced-by-glucocorticoid-associated-endoplasmic-reticulum-stress-in-rat-osteonecrosis-of-the-femoral-head-via-the-akt-bad-bcl-2-signal-pathway
#6
Shi-Cong Tao, Ting Yuan, Bi-Yu Rui, Zhen-Zhong Zhu, Shang-Chun Guo, Chang-Qing Zhang
An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material...
2017: Theranostics
https://www.readbyqxmd.com/read/28245285/the-platelet-derived-growth-factor-receptor-stat3-signaling-pathway-regulates-the-phenotypic-transition-of-corpus-cavernosum-smooth-muscle-in-rats
#7
Jun-Feng Yan, Wen-Jie Huang, Jian-Feng Zhao, Hui-Ying Fu, Gao-Yue Zhang, Xiao-Jun Huang, Bo-Dong Lv
Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28242694/receptor-interacting-protein-kinase-3-promotes-platelet-activation-and-thrombosis
#8
Yiwen Zhang, Jian Zhang, Rong Yan, Jingluan Tian, Yang Zhang, Jie Zhang, Mengxing Chen, Qingya Cui, Lili Zhao, Renping Hu, Miao Jiang, Zhenyu Li, Changgeng Ruan, Sudan He, Kesheng Dai
Previous studies have shown that receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes, including necroptosis, apoptosis, and inflammation. Here we show that RIP3 plays a critical role in regulating platelet functions and in vivo thrombosis and hemostasis. Tail bleeding times were significantly longer in RIP3-knockout (RIP3(-/-)) mice compared with their wild-type (WT) littermates. In an in vivo model of arteriole thrombosis, mice lacking RIP3 exhibited prolonged occlusion times...
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28237515/adiporon-an-adiponectin-receptor-agonist-attenuates-pdgf-induced-vsmc-proliferation-through-inhibition-of-mtor-signaling-independent-of-ampk-implications-toward-suppression-of-neointimal-hyperplasia
#9
Arwa Fairaq, Noha M Shawky, Islam Osman, Prahalathan Pichavaram, Lakshman Segar
Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due to its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK)...
February 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28220122/nf-%C3%AE%C2%BAb-links-tlr2-and-par1-to-soluble-immunomodulator-factor-secretion-in-human-platelets
#10
Pauline Damien, Fabrice Cognasse, Bernard Payrastre, Sherry L Spinelli, Neil Blumberg, Charles-Antoine Arthaud, Marie-Ange Eyraud, Richard P Phipps, Archibald McNicol, Bruno Pozzetto, Olivier Garraud, Hind Hamzeh-Cognasse
The primary toll-like receptor (TLR)-mediated immune cell response pathway common for all TLRs is MyD88-dependent activation of NF-κB, a seminal transcription factor for many chemokines and cytokines. Remarkably, anucleate platelets express the NF-κB machinery, whose role in platelets remains poorly understood. Here, we investigated the contribution of NF-κB in the release of cytokines and serotonin by human platelets, following selective stimulation of TLR2 and protease activated receptor 1 (PAR1), a classical and non-classical pattern-recognition receptor, respectively, able to participate to the innate immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#11
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28194217/schisandra-chinensis-and-morus-alba-synergistically-inhibit-in-vivo-thrombus-formation-and-platelet-aggregation-by-impairing-the-glycoprotein-vi-pathway
#12
Dong-Seon Kim, Muhammad Irfan, Yoon-Young Sung, Seung Hyung Kim, Sun Haeng Park, Young Hyun Choi, Man Hee Rhee, Ho Kyoung Kim
Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca(2+)] i release assays were carried out...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28170176/exosomes-derived-from-akt-modified-human-umbilical-cord-mesenchymal-stem-cells-improve-cardiac-regeneration-and-promote-angiogenesis-via-activating-platelet-derived-growth-factor-d
#13
Jie Ma, Yuanyuan Zhao, Li Sun, Xiaochun Sun, Xiaosu Zhao, Xiaoxian Sun, Hui Qian, Wenrong Xu, Wei Zhu
We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well known that the activation of Akt is involved in stem cell-induced cardioprotection. In the present study, we investigated whether exosomes released from Akt-overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt-hucMSCs) by using an adenovirus transfection system...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28135581/smooth-muscle-cell-targeted-rna-aptamer-inhibits-neointimal-formation
#14
William H Thiel, Carla L Esposito, David D Dickey, Justin P Dassie, Matthew E Long, Joshua Adam, Jennifer Streeter, Brandon Schickling, Maysam Takapoo, Katie S Flenker, Julia Klesney-Tait, Vittorio de Franciscis, Francis J Miller, Paloma H Giangrande
Inhibition of vascular smooth muscle cell (VSMC) proliferation by drug eluting stents has markedly reduced intimal hyperplasia and subsequent in-stent restenosis. However, the effects of antiproliferative drugs on endothelial cells (EC) contribute to delayed re-endothelialization and late stent thrombosis. Cell-targeted therapies to inhibit VSMC remodeling while maintaining EC health are necessary to allow vascular healing while preventing restenosis. We describe an RNA aptamer (Apt 14) that functions as a smart drug by preferentially targeting VSMCs as compared to ECs and other myocytes...
April 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28120218/platelet-rich-plasma-inhibits-inflammatory-factors-and-represses-rheumatoid-fibroblast-like-synoviocytes-in-rheumatoid-arthritis
#15
Shichao Tong, Ji Liu, Changqing Zhang
Rheumatoid arthritis (RA) is a chronic disease affecting daily life of numerous patients, and uncontrolled proliferation of synovial fibroblasts plays vital role during the pathology of RA. Platelet-rich plasma (PRP), widely used in tissue regeneration and pain management, is rarely studied in RA. This study aims to investigate the effect of PRP on synovial fibroblasts during RA. Rheumatoid fibroblast-like synoviocyte MH7A cells were stimulated by lipopolysaccharide (LPS) to simulate RA conditions and treated with PRP, after that the concentration of inflammatory factors interleukin (IL) 1β, tumor necrosis factor alpha (TNFα) and IL6 in the supernatant of culture medium was quantified by ELISA...
January 24, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28115185/plasma-kallikrein-enhances-platelet-aggregation-response-by-subthreshold-doses-of-adp
#16
Tatiana F Ottaiano, Sheila S Andrade, Cleide de Oliveira, Mariana C C Silva, Marcus V Buri, Maria A Juliano, Manoel J B C Girão, Misako U Sampaio, Alvin H Schmaier, Alexander Wlodawer, Francisco H A Maffei, Maria Luiza V Oliva
Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbβ3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbβ3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway...
April 2017: Biochimie
https://www.readbyqxmd.com/read/28072855/sdf-1%C3%AE-cxcr4-signaling-in-lipid-rafts-induces-platelet-aggregation-via-pi3-kinase-dependent-akt-phosphorylation
#17
Hiroko Ohtsuka, Tomohiro Iguchi, Moyuru Hayashi, Mizuho Kaneda, Kazuko Iida, Motoyuki Shimonaka, Takahiko Hara, Morio Arai, Yuichi Koike, Naomasa Yamamoto, Kohji Kasahara
Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway)...
2017: PloS One
https://www.readbyqxmd.com/read/28054640/honokiol-as-a-specific-collagen-receptor-glycoprotein-vi-antagonist-on-human-platelets-functional-ex-vivo-and-in-vivo-studies
#18
Tzu-Yin Lee, Chao-Chien Chang, Wan-Jung Lu, Ting-Lin Yen, Kuan-Hung Lin, Pitchairaj Geraldine, Jiun-Yi Li, Joen-Rong Sheu
Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca(+2) ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28011478/validation-of-vx2-as-a-hepatocellular-carcinoma-model-comparison-of-the-molecular-reaction-of-vx2-and-hepg2-tumor-cells-to-sorafenib-in-vitro
#19
COMPARATIVE STUDY
Norbert Nass, Sebastian Streit, Christian Wybranski, Julian Jürgens, Jan Brauner, Nadine Schulz, Maciej Powerski, Jens Ricke, Thomas Kalinski, Oliver Dudeck, Max Seidensticker
As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1β (IL1β)...
2017: Anticancer Research
https://www.readbyqxmd.com/read/27983763/the-common-dietary-flavonoid-myricetin-attenuates-liver-fibrosis-in-carbon-tetrachloride-treated-mice
#20
Yan Geng, Qing Sun, Wang Li, Zhen-Ming Lu, Hong-Yu Xu, Jin-Song Shi, Zheng-Hong Xu
SCOPE: Myricetin is found in most berries, vegetables, and various medicinal herbs, which has been reported to possess various bio-activities. However, the role of myricetin on liver fibrosis remains to be elucidated. METHODS AND RESULTS: Hepatic stellate cell (HSC) line CFSC-8B was stimulated by transforming growth factor-β1 (TGF-β1) or Platelet-derived growth factor-BB (PDGF-BB) to induce liver fibrosis in vitro. The results showed that myricetin significantly ameliorated TGF-β1 or PDGF-BB induced HSCs activation, cell migration, and extracellular matrix (ECM) production, blocked TGF-β1 induced phosphorylation of Smad2, P38, extracellular signal-regulated kinase (ERK) and Protein kinase B (AKT), and down-regulated PDGF-BB stimulated phosphorylation of ERK and AKT in HSCs in a dose-dependent manner...
December 16, 2016: Molecular Nutrition & Food Research
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