Excessive wall stretch of distensible hollow organs in cardiovascular and urinary systems can activate matrix metalloproteinases (MMPs), thereby releasing matrix neoepitopes and growth factor ligands, leading to ERK1/2 activation. However, the role of MMPs in mechanotransduction of ERK1/2 signaling in the bladder is unknown. We examined bladders undergoing sustained distension over time, which provides a novel platform for smooth muscle mechanotransduction studies. Bladder distension ex vivo caused increased proliferation and MMP activity. Conditioned medium from distended compared with undistended bladders induced proliferation in bladder smooth muscle cells (BSMCs). When conditioned medium from distended bladders was used to proteolyze collagen type I matrices, matrices augmented BSMC proliferation, which was inhibited if bladders were distended in presence of broad-spectrum MMP inhibitors. Distension of ex vivo bladders also induced ERK1/2 phosphorylation in situ, which was dependent on MMP activity in the intact bladder. Similarly, stretching BSMCs in vitro induced increases in ERK1/2 activation and ERK1/2-dependent proliferation under discrete mechanical conditions, and distension conditioned medium itself induced The mechanical design of distensible hollow organs such as the heart, vessels, and urinary bladder allows for stretching the wall of the organ to permit filling and contraction to facilitate accommodation and propulsion of fluid. Muscle cells in these organs are responsive to stretch in their microenvironment. Mechanotransduction in the heart and vessels involves growth factor release and activation of a number of signaling cascades. In particular, stretch activation of the mitogen-activated protein (MAP) kinase (MAPK) family can modulate cell proliferation, apoptosis, integrity of the extracellular matrix (ECM), muscle wall development, and homeostasis. As in the heart, partial obstruction and distension models that create excessive bladder wall stretch are used to mimic clinical pathological conditions. These models have shown increased muscle growth, accumulation of ECM structural components such as fibrillar collagen types I and III, 1 and increased matrix metalloproteinase (MMP) activity.
2Appreciation of MMP function has evolved significantly since their description as interstitial collagenases. MMPs exert pleiotropic influences by virtue of their ability to cleave diverse substrates, including not only structural ECM proteins but also growth-factor receptors and pre-
Background/Aims: Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links. Methods: 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity. Results: 54% of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9) years and the mean BMI (SD) was 28.1 (5.4) kg/m2. From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p < 0.05). Adipokine levels were not associated with functional outcome scores. Conclusions: The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets.
This study aimed to assess seminal mast cells in infertile men associated with varicocele (Vx) pre- and post-surgical repair. Forty-five infertile men associated with Vx were subjected to history taking and clinical examination. In addition, semen parameters and seminal mast cells stained with 1% toluidine blue were estimated pre-varicocelectomy and three months post-varicocelectomy. Vx surgical repair revealed a significant improvement in the mean sperm concentration, progressive sperm motility, total sperm motility and sperm abnormal morphology and a significant decrement in seminal mast cells (mean ± SD, 3.56 ± 2.23 cells per high-power field (HPF) vs. 2.22 ± 1.06 cells per HPF, p = .01). The pre-operative mean mast cell count demonstrated significant increases in cases with Vx grade III compared with other Vx grades and in cases with bilateral Vx compared with unilateral Vx cases. Seminal mast cells demonstrated a significant correlation with sperm concentration, progressive sperm motility and total sperm motility and a nonsignificant correlation with age and sperm abnormal morphology. It is concluded that seminal mast cells decrease significantly in infertile men with Vx after surgical repair showing a significant negative correlation with sperm concentration, progressive sperm motility and total sperm motility.
IntroductionT regulatory cells (Treg) play an important role in the maintenance of immune cell homeostasis, as it has been reported that CD4+CD25+ T cells suppress the auto-reactive responses in autoimmune diseases such as systemic lupus erythematosus (SLE). The clinical significance of the recently identified population of CD4+CD25-Foxp3+ T cells and whether they are associated with particular organ involvement is still not clear. So, the aim of our study was to evaluate the presence of CD4+CD25-Foxp3+ cells in SLE patients in comparison to healthy controls and to determine whether their frequency is associated with disease activity and particular clinical manifestations in these SLE patients.Material and methodsThe frequency of CD4+CD25-Foxp3+ T cells was analyzed in 56 female SLE patients and 30 healthy female control subjects, using flow cytometry (FACS). CD4+CD25-Foxp3+ T cells were correlated with clinical and laboratory data and the SLE Disease Activity Index (SLEDAI).ResultsThe level of CD4+CD25-Foxp3+ T cells was significantly increased in SLE patients (15.57 ±4.32%) as compared with the control group (2.46 ±0.65%). A significant correlation was observed for the percentage of CD4+CD25-Foxp3+ T cells with clinical disease activity scores and disease duration (r = 0.6, p < 0.001; r = 0.3, p = 0.02 respectively). It was also positively correlated with renal impairment and hematological involvement.ConclusionsSystemic lupus erythematosus patients exhibited an altered level of their CD4+Foxp3+ T cells with increased levels of CD4+CD25-Foxp3+ cells.
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