Search results for "SMOOTH"
showing 10 items of 710 documents
Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.
2018
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt(−)). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt(−) tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol a…
Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma : the oncogenic role of the ligands
2017
Altres ajuts: This work was supported by grants from Institut Català d'Oncologia (ICO), Instituto de Salud Carlos III (RTICC-RD12/0036/0016, /0020, /0035, /0057; and PI14/00647), Fundació A BOSCH, Fundació Amics Joan Petit, ajuts predoctorals del VHIR and RIS3CAT grants COMRDI15-1-0014 (ACCIÓ and FEDER). Altres ajuts: FEDER/COMRDI15-1-0014 Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional …
Type 5 phosphodiesterase (PDE5) and the vascular tree: from embryogenesis to aging and disease
2020
Highlights • Vascular development depends on the timely differentiation of endothelial and smooth muscle cells, that mutually influence their developmental fate. • Endothelial and vascular smooth muscle cell (VSMC) compartments can mutually influence cell and tissue modifications during vascular aging and in vascular disease. • Keeping in mind that PDE5 is mainly expressed in VSMCs, we surveyed the literature on the role of PDE5 in vascular development, aging and disease. • Although most results have been obtained by PDE5 pharmacological inhibition, no data are available, to date, on vascular development, aging or disease following PDE5 genetic ablation.
Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarc…
2019
Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. Methods and results The mechanisms underlying Shh pathway func…
Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma
2016
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrin…
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms
2019
AbstractAneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMC…
TRPM8 Channel Activation Reduces the Spontaneous Contractions in Human Distal Colon
2020
The transient receptor potential-melastatin 8 (TRPM8) is a non-selective Ca2+-permeable channel, activated by cold, membrane depolarization, and different cooling compounds. TRPM8 expression has been found in gut mucosal, submucosal, and muscular nerve endings. Although TRPM8 plays a role in pathological conditions, being involved in visceral pain and inflammation, the physiological functions in the digestive system remain unclear as yet. The aims of the present study were: (i) to verify the TRPM8 expression in human distal colon
Angiotensin II type II receptors and colonic dysmotility in 2,4-dinitrofluorobenzenesulfonic acid-induced colitis in rats
2016
Background: Angiotensin II (Ang II), the main peptide of the renin-angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAS has emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis the functionality of RAS and its contribution to colonic motor alterations. Methods: The effects of Ang II on the longitudinal colonic muscular contractility of control and DNBS-treated rats were characterized in vitro. Transcripts encoding for Ang II receptors were investigated by RT-PCR. Key Results: Inflamed preparations showed a l…
Opposite effects of dopamine on the mechanical activity of circular and longitudinal muscle of human colon.
2020
Background Because dopamine (DA) has gained increasing evidence as modulator of gut motility, we aimed to characterize dopaminergic response in human colon, evaluating function and distribution of dopamine receptors in circular vs longitudinal muscle strips. Methods Mechanical responses to DA and dopaminergic agonists on slow phasic contractions and on basal tone were examined in vitro as changes in isometric tension. RT-PCR was used to reveal the distribution of dopaminergic receptors. Key results In spontaneous active circular muscle, DA induced an increase in the amplitude of slow phasic contractions and of the basal tone, via activation of D1-like receptors. DA contractile responses wer…
JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study
2018
BackgroundPulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation (V)/perfusion (Q) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown.ObjectiveThe study of JAK2 as potential target to treat PH in IPF.Methods and resultsJAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P<0.00…