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Mechanical Stretch (mechanical + stretch)

Distribution by Scientific Domains

Medical Sciences	60%
Life Sciences	40%

Selected Abstracts

Mechanical stretch induces TGF-, synthesis in hepatic stellate cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2004
R. Sakata
Abstract Background, It is known that mechanical stress induces extracellular matrix via transforming growth factor-, (TGF-,) synthesis in vascular smooth muscle cells. Activated hepatic stellate cells (HSCs) are an important source of TGF-, in the liver. However, it remains unclear whether mechanical stress induces TGF-, in HSCs. The Rho small GTP-binding protein (Rho) has recently emerged as an important regulator of actin and cytoskeleton. We examined whether TGF-, is expressed in stretched HSCs and whether Rho is involved in stretch-induced TGF-, synthesis. Materials and methods, A cultured human HSC cell line, LI90, was used for this study. Hepatic stellate cells were cyclically stretched using the Flexercell® strain unit. Concentration of TGF-, in the conditioned medium was estimated by a bioassay using mink lung epithelial cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Transforming growth factor-, mRNA expression of HSCs was estimated by a reverse-transcription polymerase chain reaction. Replication-defective adenoviral vectors expressing a dominant negative type of Rho was utilized to suppress its effect on HSCs. Results, Transforming growth factor-, concentration of the conditioned media of stretched HSCs showed time-dependent increases as compared to nonstretched HSCs from 2 h to 24 h. Transforming growth factor-, mRNA expression in stretched HSCs was increased compared with that in nonstretched HSCs. Transfection of dominant negative Rho inhibited the stretch-induced TGF-, synthesis. Conclusions, Mechanical stretch enhanced TGF-, expression on mRNA and protein level in HSCs. Rho was closely related to stretch-induced TGF-, synthesis in HSCs. [source]

Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 during cardiac remodelling in rats

ACTA PHYSIOLOGICA, Issue 1 2010
E. Mustonen
Abstract Aim:, Accumulating evidence supports the concept that proinflammatory cytokines play an essential role in the failing heart. We examined the concomitant tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 expression in myocytes in vitro as well as in vivo in cardiac remodelling. Methods:, We assessed TWEAK and its receptor Fn14 expression in response to angiotensin (Ang) II, myocardial infarction (MI) as well as to local adenovirus-mediated p38 gene transfer in vivo. The effect of various hypertrophic factors and mechanical stretch was studied in neonatal rat ventricular myocyte cell culture. Results:, Ang II increased Fn14 levels from 6 h to 2 weeks, the greatest increase in mRNA levels being observed at 6 h (6.3-fold, P < 0.001) and protein levels at 12 h (4.9-fold, P < 0.01). TWEAK mRNA and protein levels remained almost unchanged during Ang II infusion. Likewise, a rapid and sustained elevation of Fn14 mRNA and protein levels in the left ventricle was observed after experimental MI. Moreover, local p38 gene transfer increased Fn14 mRNA and protein but not TWEAK levels. Fn14 immunoreactive cells were mainly proliferating non-myocytes in the inflammation area while TWEAK immunoreactivity localized to cardiomyocytes and endothelial cells of the coronary arteries. Hypertrophic agonists and lipopolysaccharide increased Fn14 but not TWEAK gene expression in neonatal rat myocytes, while mechanical stretch upregulated Fn14 and downregulated TWEAK gene expression. Conclusions:, In conclusion, the cardiac TWEAK/Fn14 pathway is modified in response to myocardial injury, inflammation and pressure overload. Furthermore, our findings underscore the importance of Fn14 as a mediator of TWEAK/Fn14 signalling in the heart and a potential target for therapeutic interventions. [source]

The role of oxytocin and regulation of uterine oxytocin receptors in pregnant marsupials

EXPERIMENTAL PHYSIOLOGY, Issue 2000
Laura J. Parry
The oxytocin-like peptide of most Australian marsupials is mesotocin, which differs from oxytocin by a single amino acid. This substitution has no functional significance as both peptides have equivalent affinity for and biological activity on the marsupial oxytocin-like receptor. A role for mesotocin in marsupial parturition has been demonstrated in the tammar wallaby where plasma mesotocin concentrations increase less than one minute before birth. Infusion of an oxytocin receptor antagonist at the end of gestation disrupts normal parturition, probably by preventing mesotocin from stimulating uterine contractions. In the absence of mesotocin receptor activation, a peripartum surge in prostaglandins is delayed which suggests a functional relationship between mesotocin, prostaglandin release and luteolysis. Female marsupials have anatomically separate uteri and in monovular species, such as the tammar wallaby, only one uterus is gravid with a single fetus whereas the contralateral uterus remains non-gravid. We have used this unique animal model to differentiate systemic and fetal-specific factors in the regulation of uterine function during pregnancy. The gravid uterus in the tammar wallaby becomes increasingly sensitive to mesotocin as gestation proceeds, with the maximum contractile response observed at term. This is reflected in a large increase in mesotocin receptor concentrations in the gravid uterus, and a downregulation in the non-gravid uterus in late pregnancy. The upregulation in myometrial mesotocin receptors is pregnancy-specific and independent of systemic steroids. One factor that may influence mesotocin receptor upregulation in the gravid uterus in late pregnancy is mechanical stretch of the uterus caused by the growing fetus. Our data highlight that a local fetal influence is more important than systemic factors in the regulation of mesotocin receptors in the tammar wallaby. [source]

Sensor Mechanism and Afferent Signal Transduction of the Urinary Bladder: Special Focus on transient receptor potential Ion Channels

LUTS, Issue 2 2010
Masayuki TAKEDA
In the urine storage phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter A, - and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous; however, a wide range of ion channels (e.g. TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes: TRPV (Vanilloid), TRPC (Canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction. [source]