Journal of Smooth Muscle Research最新文献

Mechanical stress underlies most aspects of cell and organismal biology. Mechanomedicine is a field of biology that seeks to understand molecular, cellular, tissue, organ, and individual responses to mechanical stimuli and aims to apply the gained knowledge to improve health. Combining biology and engineering, we explore research areas including mechanosensitive ion channels, heart failure, and regenerative medicine.This review will describe our findings in mechanobiology, our establishment of a joint venture business as we developed devices responding to medical needs, and our alliance with other companies.

Electrogastrograms (EGGs) were recorded from 16 locations on the thoraco-abdominal surface to find the maximum absolute power foci during rest (RAP) and the maximum ratio of the % content during the mirror drawing test (MDT) compared to that during rest (%C-MDT/R) for both the 3 cpm (2.4-4.9) and 6 cpm (5.0-7.4) groups. The maximum foci were obtained from control subjects and those who received gastro-intestinal surgery via total gastrectomy (TG), distal gastrectomy (DG), and total esophagectomy with colonic replacement (CR). The control mean of the infraumbilical channels 10-16 (I) expressed as %C-MDT/R of the 3 cpm group was higher than the mean of the supraumbilical channels 1-9 (S) (I>S, P<0.001). The maximum focus of the 3-cpm %C-MDT/R was in the left umbilical area, while that of the 6-cpm %C-MDT/R was found bilaterally in the right epigastric and left umbilical areas, interposed by the lower %C-MDT/R gastric area. Therefore, the presence of gastric EGG inhibition and colonic facilitation are suggested to occur during MDT. In TG and DG, the foci of the %C-MDT/R in the 3-cpm group were located bilaterally in the right epigastric and left umbilical areas. The shifts of foci suggest colonic EGG facilitation. The mean S of the 3-cpm group was significantly higher than the mean I with CR (S>I, P<0.05). The maximum foci of the 3- and 6-cpm groups were in the epigastrium. These results suggest colonic EGG facilitation in the epigastrium, as the stomach has been removed and the original gastric location is instead occupied by the transverse colon in CR.

Pompe disease (OMIM 232300) is an autosomal recessive disorder caused by mutations in the gene encoding acid α-glucosidase (GAA) (EC 3.2.1.20), the enzyme responsible for hydrolyzing lysosomal glycogen. The primary cellular pathology is lysosomal glycogen accumulation in cardiac muscle, skeletal muscle, and motor neurons, which ultimately results in cardiorespiratory failure. However, the severity of pathology and its impact on clinical outcomes are poorly described in smooth muscle. The advent of enzyme replacement therapy (ERT) in 2006 has improved clinical outcomes in infantile-onset Pompe disease patients. Although ERT increases patient life expectancy and ventilator free survival, it is not entirely curative. Persistent motor neuron pathology and weakness of respiratory muscles, including airway smooth muscles, contribute to the need for mechanical ventilation by some patients on ERT. Some patients on ERT continue to experience life-threatening pathology to vascular smooth muscle, such as aneurysms or dissections within the aorta and cerebral arteries. Better characterization of the disease impact on smooth muscle will inform treatment development and help anticipate later complications. This review summarizes the published knowledge of smooth muscle pathology associated with Pompe disease in animal models and in patients.

Background: Ex situ analyses of human myometrial tissue has been used to investigate the regulation of uterine quiescence and transition to a contractile phenotype. Following concerns about the validity of cultured primary cells, we examined whether myometrial tissue undergoes culture-induced changes ex situ that may affect the validity of in vitro models.

Objectives: To determine whether human myometrial tissue undergoes culture-induced changes ex situ in Estrogen receptor 1 (ESR1), Prostaglandin-endoperoxide synthase 2 (PTGS2) and Oxytocin receptor (OXTR) expression. Additionally, to determine whether culture conditions approaching the in vivo environment influence the expression of these key genes.

Methods: Term non-laboring human myometrial tissues were cultured in the presence of specific treatments, including; serum supplementation, progesterone and estrogen, cAMP, PMA, stretch or NF-κB inhibitors. ESR1, PTGS2 and OXTR mRNA abundance after 48 h culture was determined using quantitative RT-PCR.

Results: Myometrial tissue in culture exhibited culture-induced up-regulation of ESR1 and PTGS2 and down-regulation of OXTR mRNA expression. Progesterone prevented culture-induced increase in ESR1 expression. Estrogen further up-regulated PTGS2 expression. Stretch had no direct effect, but blocked the effects of progesterone and estrogen on ESR1 and PTGS2 expression. cAMP had no effect whereas PMA further up-regulated PTGS2 expression and prevented decline of OXTR expression.

Conclusion: Human myometrial tissue in culture undergoes culture-induced gene expression changes consistent with transition toward a laboring phenotype. Changes in ESR1, PTGS2 and OXTR expression could not be controlled simultaneously. Until optimal culture conditions are determined, results of in vitro experiments with myometrial tissues should be interpreted with caution.

Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles.

The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This review summarises the role of prostatic interstitial cells (PICs) in the generation of the spontaneous tone in the prostate. It presents current knowledge of the role of Ca²⁺ plays in PIC pacemaking, as well as the mechanisms by which this spontaneous activity triggers slow wave generation and stromal contraction. PICs display a small T-type Ca²⁺ current (I_CaT) and a large L-type Ca²⁺ current (I_CaL). In contrast to other interstitial cells in the urinary and gastrointestinal tracts, spontaneous Ca²⁺ signalling in PICs is uniquely dependent on Ca²⁺ influx through I_CaL channels. A model of prostatic pacemaking is presented describing how I_CaL can be triggered by an initial membrane depolarization evoked upon the selective opening of Ca²⁺-activated Cl^- channels by Ca²⁺ flowing only through I_CaT channels. The resulting current flow through I_CaL results in release of Ca²⁺ from internal stores and the summation of Cl^--selective spontaneous transient depolarizations (STDs) to form pacemaker potentials that propagate passively into the prostatic stroma to evoke regenerative action potentials and excitation-contraction coupling.

Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca²⁺-mediated phosphorylation of myosin light chain (MLC), contractile agonists also enhance MLC phosphorylation level, Ca²⁺-independently, by inactivating MLC phosphatase (MLCP), called Ca²⁺ sensitization of contraction, in smooth muscle cells including airways. To date, involvements of RhoA/ROCKs and PKC/Ppp1r14a (also called as CPI-17) pathways in the Ca²⁺ sensitization have been identified. Our previous studies revealed that the agonist-induced Ca²⁺ sensitization of contraction is markedly augmented in BSMs of animal models of allergen-induced AHR. In BSMs of these animal models, the expression of RhoA and CPI-17 proteins were significantly increased, indicating that both the Ca²⁺ sensitizing pathways are augmented. Interestingly, incubation of BSM cells with asthma-associated cytokines, such as interleukin-13 (IL-13), IL-17, and tumor necrosis factor-α (TNF-α), caused up-regulations of RhoA and CPI-17 in BSM cells of naive animals and cultured human BSM cells. In addition to the transcription factors such as STAT6 and NF-κB activated by these inflammatory cytokines, an involvement of down-regulation of miR-133a, a microRNA that negatively regulates RhoA translation, has also been suggested in the IL-13- and IL-17-induced up-regulation of RhoA. Thus, the Ca²⁺ sensitizing pathways and the cytokine-mediated signaling including microRNAs in BSMs might be potential targets for treatment of allergic asthma, especially the AHR.

A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness to stimuli. Cellular MLCP activity is negatively and positively regulated in response to G-protein activation and cAMP/cGMP production, respectively, through the MYPT1 regulatory subunit and an endogenous inhibitor protein named CPI-17. In this article we review the outcomes from two decade of research on the CPI-17 signaling and discuss emerging paradoxes in the view of signaling pathways regulating smooth muscle functions through MLCP.

The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO₂) for 60 days. Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO₂ to stabilize mast cell membranes. The second group (control) was not treated. Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation. Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats. The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats. Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats. This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons.

The skin of the lemur nose tip (rhinarium) has arterioles in the outer vascular plexus that are endowed with an unusual coat of smooth muscle cells. Comparison with the arterioles of the same area in a number of unrelated mammalians shows that the lemur pattern is unique. The vascular smooth muscle cells belong to the synthetic type. The function of synthetic smooth muscles around the terminal vessels in the lemur rhinarium is unclear but may have additional functions beyond regulation of vessel diameter.