Abstract:
BACKGROUND AND PURPOSE:The sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behaviour in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly elucidated. Thus, we investigated the effect of Shh on the regulation of mESC behaviour as well as the effect of Shh-pretreated mESCs in skin wound healing. EXPERIMENTAL APPROACH:The underlying mechanisms of Shh signalling pathway in growth and motility of mESCs were investigated using Western blot analysis, a cell proliferation assay and cell migration assay. In addition, the effect of Shh-pretreated mESCs in skin wound healing was determined using a mouse excisional wound splinting model. KEY RESULTS:Shh disrupted the adherens junction through proteolysis by activating MMPs. In addition, the release of β-catenin from adherens junctions mediated by Shh led to cell cycle-dependent mESC proliferation. Shh-mediated Gli1 expression led to integrin β1 up-regulation, followed by FAK and Src phosphorylation. Furthermore, among the Rho-GTPases, Rac1 and Cdc42 were activated in a Shh-dependent manner while F-actin expression was suppressed by Rac1 and Cdc42 siRNA transfection. Consistent with the in vitro results, the skin wound healing assay revealed that Shh-treated mESCs increased angiogenesis and skin wound repair compared to that in Shh-treated mESCs transfected with integrin β1 siRNA in vivo. CONCLUSIONS AND IMPLICATIONS:Our results imply that Shh induces adherens junction disruption and integrin β1-dependent F-actin formation by a mechanism involving FAK/Src and Rac1/Cdc42 signalling pathways in mESCs.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Oh JY,Suh HN,Choi GE,Lee HJ,Jung YH,Ko SH,Kim JS,Chae CW,Lee CK,Han HJdoi
10.1111/bph.14423subject
Has Abstractpub_date
2018-09-01 00:00:00pages
3548-3562issue
17eissn
0007-1188issn
1476-5381journal_volume
175pub_type
杂志文章abstract::Adenosine alone at 0.1 and 1.0 mg per tracheal segment stimulated mucus secretion by 52% and 88%, respectively, compared to baseline (P less than 0.0001). The site of the potent secretagogue effect of adenosine in canine trachea was consistent with A2 activation. A2 site activation and enhanced secretion were also ind...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb09435.x
更新日期:1985-09-01 00:00:00
abstract::1 The fate of (15S)-15-methyl prostaglandin E(2) methyl ester and 16,16-dimethyl prostaglandin E(2) in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E(2) by means of bioassay.2 Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08456.x
更新日期:1978-02-01 00:00:00
abstract::1 Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation. 2 The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences. 3 Changes in the ionic environment of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb13665.x
更新日期:1979-06-01 00:00:00
abstract::1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07661.x
更新日期:1976-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:7-Ketocholesterol, an oxysterol present in atherosclerotic lesions, induces smooth muscle cell (SMC) death, thereby destabilizing plaques. Statins protect patients from myocardial infarction, though they induce SMC apoptosis. We investigated whether statins and 7-ketocholesterol exerted additive ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.181
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In humans and non-human primates, the 7TM receptor GPR17 exists in two isoforms differing only by the length of the N-terminus. Of these, only the short isoform has previously been characterized. Hence, we investigated gene expression and ligand-binding profiles of both splice variants and furthe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00633.x
更新日期:2010-03-01 00:00:00
abstract::Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.01177.x
更新日期:2011-12-01 00:00:00
abstract::1. To examine further the potentiation by endothelin-1 on the vascular response to sympathetic stimulation, we studied the isometric response of isolated segments, 2 mm long, from the rabbit central ear artery to electrical field stimulation (1-8 Hz), under different conditions, at 37 degrees C and during cooling (30 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701324
更新日期:1997-08-01 00:00:00
abstract::1. This study investigated the importance of renal sympathetic nerves in regulating sodium and water excretion from the kidneys of stroke prone spontaneously hypertensive and 2K1C Goldblatt hypertensive rats anaesthetized with chloralose/urethane (17.5/300 mg initially and supplemented at regular intervals), and prepa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15621.x
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01794.x
更新日期:2012-06-01 00:00:00
abstract::1. alpha 1-Adrenoceptor subtypes in rabbit thoracic aorta have been examined in binding and functional experiments. 2. [3H]-prazosin bound to two distinct populations of alpha 1-adrenoceptors (pKD,high = 9.94, Rhigh = 79.2 fmol mg-1 protein; pKD,low = 8.59, Rlow = 215 fmol mg-1 protein). Pretreatment with chloroethylc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13507.x
更新日期:1993-04-01 00:00:00
abstract::1. [3H]-ouabain uptake in resting guinea-pig papillary muscles depended directly on incubation time and inversely with muscle radius. The equivalence of both parameters support the relevance of diffusion. A particular mechanism of receptor-controlled diffusion was implicated by the saturation of initial rates of uptak...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11659.x
更新日期:1988-10-01 00:00:00
abstract::1. The rat isolated superior mesenteric bed, perfused with Krebs-Henseleit solution containing 10 microM indomethacin and precontracted with 100 microM methoxamine, was used to study the vasorelaxation produced by some fragments of endothelin-1, by two alanyl-substituted analogues, and by human and porcine proendothel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12428.x
更新日期:1991-10-01 00:00:00
abstract::1 Salbutamol and disodium cromoglycate were compared for anti-anaphylactic activity against passive anaphylaxis in rat skin and peritoneum in vivo and in rat mast cells and human lung fragments in vitro.2 Salbutamol administered intravenously to rats inhibited cutaneous anaphylaxis, but also inhibited cutaneous respon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Kinins are pro-inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B(1) receptors exacerbates the development of dextran sulfate sodium (DSS)-i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02136.x
更新日期:2013-01-01 00:00:00
abstract::1. The effects of cocaine, 6-hydroxydopamine (6-OHDA), reserpine and 17-beta-oestradiol on the sensitivity of the rat anococcygeus muscle to noradrenaline (NA), acetylcholine (ACh) and KCl were investigated.2. Cocaine (10(-5)M) increased the sensitivity of the anococcygeus to NA (100-fold) but not to ACh or KCl.3. 6-O...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb17261.x
更新日期:1973-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH:Concentrations of reactive...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00704.x
更新日期:2010-06-01 00:00:00
abstract::This study was performed to characterize the receptor subtypes involved in the endothelin stimulation of phospholipase D (PLD) in rat cortical astrocytes in primary culture. PLD activity was determined by measuring the formation of [32P]phosphatidylbutanol in [32P]orthophosphate prelabelled cells stimulated in the pre...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701997
更新日期:1998-08-01 00:00:00
abstract::1 Sheep were injected with either methotrexate or melphalan in an attempt to lower the numbers of neutrophil granulocytes in peripheral blood. 2 Methotrexate, 5.0 mg/kg intravenously, on three consecutive days, produced no noticeable clinical or haematological changes. 3 A single dose of melphalan, 1.0 mg/kg intraveno...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb09758.x
更新日期:1978-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Melanin-concentrating hormone receptor 1 (MCH1 receptor) antagonists are being considered as anti-obesity agents. The present study reports a new class of MCH1 receptor antagonists with an 8-methylquinoline scaffold. The molecular mechanism of MCH1 receptor blockade by these antagonists was exami...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12529
更新日期:2014-03-01 00:00:00
abstract::Calcitonin gene-related peptide (CGRP) is believed to play a pivotal role in the pathogenesis of migraine via activation of CGRP receptors in the trigeminovascular system. The CGRP receptor antagonist, BIBN4096BS, has proven efficacy in the acute treatment of migraine attacks and represents a new therapeutic principle...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705966
更新日期:2004-11-01 00:00:00
abstract::The effects of intravenous doses of Org 6001 and disopyramide (10 mg/kg) known to confer protection against early postligation-induced arrhythmias in the anaesthetized rat when given prophylactically, were assessed following postligation administration. When given 1 min after ligation both drugs greatly reduced the in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09245.x
更新日期:1982-08-01 00:00:00
abstract::1. A study has been made of serum, mixed and parotid salivary levels attained in normal volunteers following oral dosage of 500 mg phenoxymethylpenicillin tablets, 500 mg crushed phenoxymethylpenicillin tablets in capsules, 500 mg ampicillin, 500 mg cloxacillin and 500 mg cephalexin.2. High mixed saliva levels were ob...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07173.x
更新日期:1971-09-01 00:00:00
abstract::1 In cats anaesthetized with pentobarbitone, saxitoxin and, on a few occasions, tetrodotoxin were injected into a lateral cerebral ventricle or into the subarachnoid space of the lower brain stem. Observations were made on frequency and tidal volume of breathing, on CO(2) responsiveness and on electrical responsivenes...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07561.x
更新日期:1977-12-01 00:00:00
abstract::1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have admi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14167.x
更新日期:1990-12-01 00:00:00
abstract::1. This study was undertaken to investigate whether, after a brief exposure of guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid agonist also possessing antagonist activity at mu-opioid receptors, the addition of opioid antagonists produced withdrawal contractures. Our aim was to verify in th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13334.x
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Much interest is currently being focused on the anti-nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors, including their location and mechanism of action. The purpose of this study was to elucidate these issues using 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), a nACh re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00613.x
更新日期:2010-03-01 00:00:00
abstract::1. A new series of cardiotonics based on five steroid nuclei has been evaluated for inhibition of Na-+/K-+-ATPase and Rb uptake by red blood cells, and for inotropic activity and toxicity in dogs. Structure-activity relationships are discussed. 2. The in vitro tests can be used satisfactorily to predict inotropic acti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07411.x
更新日期:1975-05-01 00:00:00
abstract::1 The influence of the epithelium on contractions produced by the peptidoleukotrienes, 5-hydroxytryptamine (5-HT) and the thromboxane mimetic, U-44069, was examined in trachea from control and ovalbumin-sensitized guinea-pigs. 2 In control tissues removal of the epithelium produced an approximately 2 to 4 fold leftwar...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11334.x
更新日期:1987-10-01 00:00:00
abstract::1. We studied the effects of various K+ channel blockers on the vasodilator responses of guinea-pig isolated basilar arteries to nitrergic nerve stimulation, the nitric oxide (NO) donor sodium nitroprusside (SNP), and the membrane permeable guanosine-3',5'-cyclic monophosphate (cyclic GMP) analogue 8-bromo-cyclic GMP ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701552
更新日期:1998-01-01 00:00:00