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https://www.readbyqxmd.com/read/28549178/rhoa-rock-inhibition-improves-the-beneficial-effects-of-glucocorticoid-treatment-in-dystrophic-muscle-implications-for-stem-cell-depletion
#1
Xiaodong Mu, Ying Tang, Koji Takayama, Wanqun Chen, Aiping Lu, Bing Wang, Kurt Weiss, Johnny Huard
Glucocorticoid treatment represents a standard palliative treatment for Duchenne muscular dystrophy (DMD) patients, but various adverse effects have limited this treatment. In an effort to understand the mechanism(s) by which glucocorticoids impart their effects on the dystrophic muscle, and potentially reduce the adverse effects, we have studied the effect of prednisolone treatment in dystrophin/utrophin double knockout (dKO) mice, which exhibit a severe dystrophic phenotype due to rapid muscle stem cell depletion...
May 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28542501/a-rho-associated-coiled-coil-containing-kinases-rock-inhibitor-y-27632-enhances-adhesion-viability-and-differentiation-of-human-term-placenta-derived-trophoblasts-in-vitro
#2
Kenichiro Motomura, Naoko Okada, Hideaki Morita, Mariko Hara, Masato Tamari, Keisuke Orimo, Go Matsuda, Ken-Ichi Imadome, Akio Matsuda, Takeshi Nagamatsu, Mikiya Fujieda, Haruhiko Sago, Hirohisa Saito, Kenji Matsumoto
Although human term placenta-derived primary cytotrophoblasts (pCTBs) represent a good human syncytiotrophoblast (STB) model, in vitro culture of pCTBs is not always easily accomplished. Y-27632, a specific inhibitor of Rho-associated coiled-coil containing kinases (ROCK), reportedly prevented apoptosis and improved cell-to-substrate adhesion and culture stability of dissociated cultured human embryonic stem cells and human corneal endothelial cells. The Rho kinase pathway regulates various kinds of cell behavior, some of which are involved in pCTB adhesion and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28540083/additive-intraocular-pressure-lowering-effects-of-ripasudil-with-glaucoma-therapeutic-agents-in-rabbits-and-monkeys
#3
Yoshio Kaneko, Masayuki Ohta, Tomoyuki Isobe, Yuto Nakamura, Ken Mizuno
Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP) by increasing conventional outflow through the trabeculae to Schlemm's canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28536952/ncam-affects-directional-lamellipodia-formation-of-bmscs-via-%C3%AE-1-integrin-signal-mediated-cofilin-activity
#4
Jia-Jia Bi, Jing Li, Bin-Feng Cheng, Hai-Jie Yang, Qiong-Qiong Ding, Rui-Fei Wang, Su-Juan Chen, Zhi-Wei Feng
The neural cell adhesion molecule (NCAM), a key member of the immunoglobulin-like CAM family, was reported to regulate the migration of bone marrow-derived mesenchymal stem cells (BMSCs). However, the detailed cellular behaviors including lamellipodia formation in the initial step of directional migration remain largely unknown. In the present study, we reported that NCAM affects the lamellipodia formation of BMSCs. Using BMSCs from Ncam knockout mice we found that Ncam deficiency significantly impaired the migration and the directional lamellipodia formation of BMSCs...
May 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28535907/suppression-of-epithelial-restitution-using-an-inhibitor-against-rho-associated-coiled-coil-containing-protein-kinase-aggravates-colitis-through-reduced-epithelial-expression-of-a-kinase-anchor-protein-13
#5
Yumi Kangawa, Toshinori Yoshida, Yutaka Yonezawa, Kiyoshi Maruyama, Shim-Mo Hayashi, Makoto Shibutani
In the gastrointestinal tract, the immediate healing response to mucosal damage is critical to sustain mucosal homeostasis. The migration of surrounding epithelial cells to cover the denuded area without proliferation is termed restitution, followed by early reparation of the damage. In this study, we determined the role of A-kinase anchor protein 13 (AKAP13) in mice with dextran sulphate sodium (DSS)-induced colitis upon mucosal injury and restitution, and investigated whether inhibition of Rho-associated coiled-coil containing protein kinase (ROCK), downstream effector of AKAP13, affects these mucosal responses...
May 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28535594/industrial-pm2-5-cause-pulmonary-adverse-effect-through-rhoa-rock-pathway
#6
Junyan Yan, Chia-Hsiang Lai, Shih-Chun Candice Lung, Chongjun Chen, Wen-Cheng Wang, Pin-I Huang, Chia-Hua Lin
According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM2.5) is associated with adverse health effects, the major action mechanisms of different compositions of PM2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM2...
May 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28534935/effect-of-fasudil-on-cognitive-function-following-status-convulsion-in-rats
#7
Rong He, Wei Han, Xiaojie Song, Xiaoju Tang, Li Cheng, Li Jiang
Fasudil has been demonstrated to possess a protective effect in neural injury; however, its protective effect on convulsive brain injury remains to be assessed. The aim of the present study was to investigate the latent mechanism and effect of fasudil on cognitive function following status convulsion (SC) in rats. Initially, to determine the effects of SC, the expression levels of Ras homolog gene family, member A (RhoA)/Rho‑associated protein kinase (ROCK) signaling pathway‑associated proteins were measured by western blot analysis in 16 rats...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28531660/carbon-black-aggregates-cause-endothelial-dysfunction-by-activating-rock
#8
Junyan Yan, Chia-Hsiang Lai, Shih-Chun Candice Lung, Wen-Cheng Wang, Chih-Ching Huang, Guan-Wen Chen, Guangli Suo, Cheng-Tai Choug, Chia-Hua Lin
Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA...
May 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28526517/regulation-of-rhoa-rock-and-sustained-arterial-contraction-by-low-cytosolic-ca-2-levels-during-prolonged-depolarization-of-arterial-smooth-muscle
#9
Cristina Porras-González, Antonio Ordóñez, Antonio Castellano, Juan Ureña
The role of L-type Ca(2+) channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca(2+) influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2...
May 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28524745/actin-cytoskeleton-regulates-functional-anchorage-migration-switch-during-t-cadherin-induced-phenotype-modulation-of-vascular-smooth-muscle-cells
#10
Agne Frismantiene, Emmanouil Kyriakakis, Boris Dasen, Paul Erne, Therese J Resink, Maria Philippova
Vascular smooth muscle cell (SMC) switching between differentiated and dedifferentiated phenotypes is reversible and accompanied by morphological and functional alterations that require reconfiguration of cell-cell and cell-matrix adhesion networks. Studies attempting to explore changes in overall composition of the adhesion nexus during SMC phenotype transition are lacking. We have previously demonstrated that T-cadherin knockdown enforces SMC differentiation, whereas T-cadherin upregulation promotes SMC dedifferentiation...
May 19, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28513223/activation-of-thromboxane-a2-receptors-mediates-endothelial-dysfunction-in-diabetic-mice
#11
Xiaona Xie, Wanchun Sun, Jun Wang, Xiaoou Li, Xiaofeng Liu, Ning Liu
BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473)...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#12
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#13
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28493326/hyperglycaemia-and-aberrated-insulin-signalling-stimulate-tumour-progression-via-induction-of-the-extracellular-matrix-component-hyaluronan
#14
Sören Twarock, Christina Reichert, Ulrike Peters, Daniel J Gorski, Katharina Röck, Jens W Fischer
Epidemiological studies have detected a higher incidence of various tumour entities in diabetic patients. However, the underlying mechanisms remain insufficiently understood. Glucose-derived pericellular and extracellular hyaluronan (HA) promotes tumour progression and development. In this study, we tested the hypothesis that a diabetic metabolic state, characterised by hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour progression via the induction of HA synthesis. In a streptozotocin-induced diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin caused an increased formation of tumour-associated HA-matrix, which in turn accelerated tumour progression and neoangiogenesis...
May 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28493050/fasudil-ameliorates-endothelial-dysfunction-in-streptozotocin-induced-diabetic-rats-a-possible-role-of-rho-kinase
#15
Amal Hofni, Basim A Shehata Messiha, Safwat A Mangoura
Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a crucial role in this setting. The present study was conducted to investigate the effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil (5 mg/kg per day) was orally administered for 8 weeks...
May 11, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28488809/optimized-isolation-and-expansion-of-human-airway-epithelial-basal-cells-from-endobronchial-biopsy-samples
#16
Kate H C Gowers, Robert E Hynds, Ricky M Thakrar, Bernadette Carroll, Martin A Birchall, Sam M Janes
Autologous airway epithelial cells have been used in clinical tissue-engineered airway transplantation procedures with a view to assisting mucosal regeneration and restoring mucociliary escalator function. However, limited time is available for epithelial cell expansion due to the urgent nature of these interventions and slow epithelial regeneration has been observed in patients. Human airway epithelial cells can be expanded from small biopsies or brushings taken during bronchoscopy procedures but the optimal mode of tissue acquisition from patients has not been investigated...
May 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28488585/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#17
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28477140/chondroitin-sulfate-impairs-neural-stem-cell-migration-through-rock-activation
#18
Layla T Galindo, Mayara T V V Mundim, Agnes S Pinto, Gabrielly M D Chiarantin, Maíra E S Almeida, Marcelo L Lamers, Alan R Horwitz, Marinilce F Santos, Marimelia Porcionatto
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site...
May 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28476048/descemetorhexis-without-grafting-for-fuchs-endothelial-dystrophy-supplementation-with-topical-ripasudil
#19
Gregory Moloney, Constantinos Petsoglou, Matthew Ball, Yves Kerdraon, Roland Höllhumer, Natasha Spiteri, Simone Beheregaray, Judith Hampson, Mario DʼSouza, Raj N Devasahayam
PURPOSE: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases. METHODS: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months...
June 2017: Cornea
https://www.readbyqxmd.com/read/28472283/oxldl-derived-lysophosphatidic-acid-promotes-the-progression-of-aortic-valve-stenosis-through-a-lpar1-rhoa-nf-%C3%AE%C2%BAb-pathway
#20
Mohamed Jalloul Nsaibia, Marie-Chloé Boulanger, Rihab Bouchareb, Ghada Mkannez, Khai Le Quang, Fayez Hadji, Deborah Argaud, Abdellaziz Dahou, Yohan Bossé, Marlys L Koschinsky, Philippe Pibarot, Benoit J Arsenault, André Marette, Patrick Mathieu
AIMS: Oxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least 6 different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve...
May 4, 2017: Cardiovascular Research
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