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Matrix Remodelling (matrix + remodelling)
Selected AbstractsOverload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6ACTA PHYSIOLOGICA, Issue 4 2009J. P. White Abstract Aim:, Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. Methods:, Male C57/BL6 (WT) and C57/BL6 × IL-6,/, (IL-6,/,) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. Result:, Plantaris muscle mass increased 59% in WT and 116% in IL-6,/, mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6,/, mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6,/, muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6,/, muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-, and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6,/, muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6,/, muscle was attenuated when compared with WT OV mice. Conclusion:, IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth. [source] Subventricular zone-derived neuroblast migration to the olfactory bulb is modulated by matrix remodellingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Serena Bovetti Abstract In the rodent brain neural progenitor cells are born in the subventricular zone and migrate along a pathway called the rostral migratory stream (RMS) into the olfactory bulb where they differentiate into several classes of interneurones. In the adult, tangential migration in the RMS takes place in ,chains' of cells contained within glial tubes. In contrast, neonatal neuroblasts along the RMS lack these defined glial tubes and chains, migrating instead as individual cells. Time-lapse confocal microscopy of neuroblasts at each of these ages shows that individual cells migrate in a saltatory manner with bursts of high speed followed by periods of slower speed. Tangential migration within a glial tube is 20% faster than migration as individual cells. Neuroblasts may also interact and modify the extracellular matrix during migration through expression of a family of proteins, the matrix metalloproteinases (MMPs). MMPs are present and active along the subventricular zone,olfactory bulb pathway. In the presence of inhibitors of MMPs, neuroblast migration rates were reduced only when cells migrate individually. Chain migration in the adult was unaffected by MMP inhibitors. Taken together, these data suggest that MMPs only influence migration as individual cells and not as chains. [source] Design of Peptide Hydroxamate-Based Photoreactive Activity-Based Probes of Zinc-Dependent MetalloproteasesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2010Paul P. Geurink Abstract Metalloproteases (ADAMs, MMPs) are multidomain proteins that play key roles in extracellular matrix remodelling and degradation, in cell,cell and cell,matrix interactions and in the proteolytic liberation of membrane-anchored proforms of cytokines and growth factors, the so-called ectodomainshedding. In this work we describe the development ofphotoactivatable activity-based probes with which active metalloproteases can be visualised. Our probes are based on the succinyl hydroxamate motif and differ in the positioning of the trifluoromethylphenyldiazirine photoreactive group. We demonstrate that directing the photoactivatable group towards the S1, pocket yields activity-based probes more effective than the corresponding probe with the photoactivatable group directed towards the S2, pocket. [source] CSRP2, TIMP-1, and SM22, promoter fragments direct hepatic stellate cell-specific transgene expression in vitro, but not in vivoLIVER INTERNATIONAL, Issue 1 2004Jens Herrmann Abstract: Background/Aims: The activation of hepatic stellate cells (HSC) and their transdifferentiation into myofibroblasts (MFB) is the key step for development of liver fibrosis. Over the past several years, significant progress has been made in the understanding of the critical pathways involved incells undergoing activation. Cellular activation in the course of transdifferentiation involves, among other biochemical modifications, functionally relevant changes in the control of gene expression. These include the up-regulation of transcription factors, different extracellular matrix proteins, cell adhesion molecules, smooth muscle specific genes, and proteins involved in matrix remodelling, or cytoskeletal organization. The corresponding regulatory elements of these genes have afforded us the opportunity to express transgenes with antifibrotic potential in a cell type- and/or transdifferentiation-dependent manner. Methods: In the present study, we have tested several promoters for their ability to mediate cell-specific expression, including those for CSRP2, SM22,, and TIMP-1 (CSRP2, gene encoding the LIM domain protein CRP2; SM22,, smooth muscle-specific gene encoding a 22-kDa protein; TIMP-1, gene encoding the tissue inhibitor of metalloproteinases-1), which in liver are specifically expressed in HSC or become strongly activated during the acute remodelling into MFB. We constructed adenoviral reporter vectors in which relevant portions of the promoters were fused to the green fluorescent protein. Results and Conclusion: Our experiments demonstrate that each of these promoters is sufficient to achieve strong or partially selective expression in vitro but none is able to direct a specific or inducible expression of transgenes in HSC/MFB in vivo. [source] Intestinal regeneration by a novel surgical procedureBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2008S.-C. Jwo Background: Treatment of short bowel syndrome is problematical. Small bowel tissue engineering has achieved modest results in animal studies. The aim of this study was to investigate intestinal regeneration in a novel surgical model. Methods: Roux-en-Y bypass procedures were performed on 40 Wistar rats weighing 250,350 g. Animals were killed at 1, 2, 3, 4, 8, 12 and 24 weeks after implantation with a 3-cm silicone tube. The spatio temporal relationship of intestinal regeneration was analysed using three-dimensional multislice computed tomography, and examination of sequential morphological changes on gross or histological findings and measurement of missing intestinal tissue (growth defects). Results: Progressive intestinal regeneration on a silicone tube was identifiable in 35 animals. Most adhesions were initially localized on the tube but spread to a distal site 4 weeks after implantation. Growth defects decreased with time, with a marked reduction in the first 4 weeks and a gradual reduction to week 24 after implantation. Luminal patency shown radiologically as well as sequential histological findings, such as mucosal lining, matrix remodelling and muscular regeneration, suggested that regeneration of intestinal tissue took place, not merely scar contraction. Conclusion: Non-invasive as well as histomorphological assessment followed intestinal regeneration over time in this model, which provides scope for further studies. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||