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SMA Expression (sma + expression)
Selected AbstractsRosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstructionNEPHROLOGY, Issue 2 2009SHAI EFRATI SUMMARY Aim: Peroxisome proliferator-activated receptor (PPAR)-, activation by rosiglitazone decreases manifestation of intrarenal inflammatory hallmarks. Inflammation significantly aggravates renal injury following urinary tract obstruction. The effect of rosiglitazone on renal inflammation following unilateral ureteral obstruction was investigated. Methods: Ninety-six Srague,Dawley rats were subjected to unilateral ureteral ligation, or to sham operation. Half of each group received rosiglitazone, 5 mg/kg bodyweight per day. The animals were killed and their kidneys allocated following 1 h, 24 h or 2 weeks, for pathological examination or for intrarenal transforming growth factor (TGF)-,, interleukin (IL)-4, IL-6, IL-10 and nitric oxide (NO) assessment by specific enzyme-linked immunosorbent assays. Apoptosis rates, extracellular matrix deposition, PPAR-,, ,-smooth muscle actin (,-SMA) expression and macrophage infiltration were assessed by specific immunohistological stainings. Results: PPAR-, receptor expression was downregulated, and infiltration of macrophages decreased, in all rosiglitazone-treated kidneys. Rosiglitazone significantly decreased apoptosis, TGF-,, IL-6, ,-SMA expression and NO availability in obstructed kidneys. Synthesis of IL-10 was unaltered, while IL-4 augmented by Rosiglitazone. Rosiglitazone also affected NO and IL-4 production in sham-operated controls. Conclusion: (i) Rosiglitazone attenuates profibrotic and pro-inflammatory responses in a rat model of ureteral obstruction-induced renal inflammation; (ii) rosiglitazone stimulates counteractive anti-inflammatory responses in the damaged kidneys; (iii) in part, rosiglitazone exerts comparable anti-inflammatory effects on obstructed kidneys and unobstructed healthy controls. Taken together, this ascertains the importance of the anti-inflammatory role of rosiglitazone treatment in amelioration of ureteral obstruction-induced renal damage. [source] Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosisNEPHROLOGY, Issue 3 2000M Katerelos SUMMARY This study examined the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and osteopontin in unilateral ureteral obstruction (UUO) in the rat, a model of obstructive uropathy. HB-EGF mRNA was upregulated 5.5-fold at 4 h post-obstruction (P < 0.05) and 4.5-fold after 12 h (P < 0.05). Immunohistochemical staining for HB-EGF demonstrated an increase in protein in the distended tubules. To determine what effects increased HB-EGF might have in the obstructed kidney, we attempted to determine whether HB-EGF upregulates osteopontin and ,-smooth muscle actin (,-SMA) in the tubular line NRK-52E. Both of these molecules are increased in UUO. Osteopontin mRNA was upregulated in NRK-52E cells after 24, 48 and 72 h HB-EGF stimulation. In contrast, HB-EGF caused a downregulation of ,-SMA protein by Western blot in NRK-52E cells. When a blocking mAb against secreted HB-EGF was administered, however, there was no effect on osteopontin mRNA levels or immunohistochemical staining for ,-smooth muscle actin. These data suggest that the action of HB-EGF in UUO may be to increase osteopontin and reduce ,-smooth muscle actin expression by tubular epithelial cells by an autocrine or intracrine mechanism. By reducing ,-SMA expression, HB-EGF may also act to maintain epithelial cell morphology in this model. [source] Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptorPHYTOTHERAPY RESEARCH, Issue 6 2009Guei-Jane Wang Abstract Hepatic fibrosis is an outcome of chronic liver diseases. The activation and proliferation of hepatic stellate cells (HSCs) is a key event in liver injury. The fruiting body of Ganoderma lucidum has long been a popular oriental medicine for treating liver diseases. The aim of this present study was to investigate the antiproliferative effects of the triterpenoid-rich extract (GLT) of G. lucidum in a cell line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor (PDGF)-BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU) incorporation. Flow cytometry using propidium iodide (PI) labeling was carried out to analyse the cell cycle distribution and apoptosis. , -Smooth muscle actin (, -SMA) was used to evaluate extracellular matrix deposition, and western blotting was performed to measure cyclins D1 and D2, and phosphorylation of the PDGF, -receptor (PDGF,R), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration-dependent manner with an IC50 of 8.52 ± 0.33 µg/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGF,R and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in , -SMA expression. These results indicated that G. lucidum inhibits PDGF-BB-activated HSC proliferation possibly through blocking PDGF,R phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis. Copyright © 2008 John Wiley & Sons, Ltd. [source] Distribution and Quantity of Contractile Tissue in Postnatal Development of Rat Alveolar InterstitiumTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2008Renée Dickie Abstract Alpha,smooth muscle actin (,-SMA) -expressing cells are important participants in lung remodeling, during both normal postnatal ontogeny and after injury. Developmental dysregulation of these contractile cells contributes to bronchopulmonary dysplasia in newborns, and aberrant recapitulation in adults of the normal ontogeny of these cells has been speculated to underlie disease and repair in mature lungs. The significance of airway smooth muscle has been widely investigated, but contractile elements within the pulmonary parenchyma, although also of structural and functional consequence in developing and mature lungs, are relatively unstudied and little quantitative information exists. Here, we quantify the areal density of ,-SMA expression in lung parenchyma and assess changes in its spatiotemporal distribution through postnatal ontogeny. Using an antibody against ,-SMA, we immunofluorescently labeled contractile elements in lung sections from a postnatal growth series of rats. Images were segmented using thresholded pixel intensity. Alpha-SMA areal density in the alveolar interstitium was calculated by dividing the area of ,-SMA,positive staining by the tissue area. The areal density of ,-SMA in 2-day neonates was 3.7%, almost doubled, to 7.2% by 21 days, and decreased to 3% in adults. Neonates had large, elongate concentrations of ,-SMA, and ,-SMA localized both at septal tips and within the interstitium. In adults, individual areas of ,-SMA expression were smaller and more round, and located predominately in alveolar ducts, at alveolar ends and bends. The results are consistent with increasing ,-SMA expression during the period of peak myofibroblast activity, corresponding to the phase of rapid alveolarization in the developing lung. Anat Rec, 291:83,93, 2007. © 2007 Wiley-Liss, Inc. [source] Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblastsARTHRITIS & RHEUMATISM, Issue 11 2009Galina S. Bogatkevich Objective Myofibroblasts are the principal mesenchymal cells responsible for tissue remodeling, collagen deposition, and the restrictive nature of lung parenchyma associated with pulmonary fibrosis. We previously reported that thrombin activates protease-activated receptor 1 (PAR-1) and induces a myofibroblast phenotype in normal lung fibroblasts resembling the phenotype of scleroderma lung myofibroblasts. We undertook this study to investigate whether a selective direct thrombin inhibitor, dabigatran, interferes with signal transduction in human lung fibroblasts induced by thrombin and mediated via PAR-1. Methods Lung fibroblast proliferation was analyzed using the Quick Cell Proliferation Assay. Expression and organization of ,-smooth muscle actin (,-SMA) was studied by immunofluorescence staining and immunoblotting. Contractile activity of lung fibroblasts was measured by a collagen gel contraction assay. Connective tissue growth factor (CTGF) and type I collagen expression was analyzed on Western blots. Results Dabigatran, at concentrations of 50,1,000 ng/ml, inhibited thrombin-induced cell proliferation, ,-SMA expression and organization, and the production of collagen and CTGF in normal lung fibroblasts. Moreover, when treated with dabigatran (1 ,g/ml), scleroderma lung myofibroblasts produced 6-fold less ,-SMA, 3-fold less CTGF, and 2-fold less type I collagen compared with untreated cells. Conclusion Dabigatran restrains important profibrotic events in lung fibroblasts and warrants study as a potential antifibrotic drug for the treatment of fibrosing lung diseases such as scleroderma lung disease and idiopathic pulmonary fibrosis. [source] | ||||||||||