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We provide the first comprehensive analysis of the extracellular matrix (ECM) composition of peri-islet capsules, composed of the peri-islet basement membrane (BM) and subjacent interstitial matrix (IM), in development of type 1 diabetes in NOD mice and in human type 1 diabetes. Our data demonstrate global loss of peri-islet BM and IM components only at sites of leukocyte infiltration into the islet. Stereological analyses reveal a correlation between incidence of insulitis and the number of islets showing loss of peri-islet BM versus islets with intact BMs, suggesting that leukocyte penetration of the peri-islet BM is a critical step. Protease- and protease inhibitor--specific microarray analyses (CLIP-CHIP) of laser-dissected leukocyte infiltrated and noninfiltrated pancreatic islets and confirmatory quantitative real time PCR and protein analyses identified cathepsin S, W, and C activity at sites of leukocyte penetration of the peri-islet BM in association with a macrophage subpopulation in NOD mice and human type 1 diabetic samples and, hence, potentially a novel therapeutic target specifically acting at the islet penetration stage. Interestingly, the peri-islet BM and underlying IM are reconstituted once inflammation subsides, indicating that the peri-islet BM-producing cells are not lost due to the inflammation, which has important ramifications to islet transplantation studies. [ABSTRACT FROM AUTHOR]

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-β 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. [ABSTRACT FROM AUTHOR]

Abstract: The matrix metalloproteinase (MMP) family of extracellular proteases is conserved throughout the animal kingdom. Studies of invertebrate MMPs have demonstrated they are involved in tissue remodeling. In Drosophila, MMPs are required for histolysis, tracheal growth, tissue invasion, axon guidance, and dendritic remodeling. Recent work demonstrates that MMPs also participate in Drosophila tumor invasion. In Caenorhabditis elegans an MMP is involved in anchor cell invasion; a Hydra MMP is important for regeneration and maintaining cell identity; and a sea urchin MMP degrades matrix to allow hatching. In worms and in flies, MMPs are regulated by the JNK pathway. [Copyright &y& Elsevier]

Abstract: Discoidin Domain Receptors (DDRs) have recently emerged as non-integrin-type receptors for collagen. The two mammalian gene products Discoidin Domain Receptor 1 and -2 constitute a subfamily of tyrosine kinase receptors that are selectively expressed in a number of different cell types and organs. Upon collagen activation, DDRs regulate cell adhesion, proliferation and extracellular matrix remodeling. Here we review the various signaling pathways and cellular responses evoked by activated DDRs. Additionally, we give an overview of the more recent advances in understanding the role of DDRs in various human diseases, in particular during tumor progression, atherosclerosis, inflammation and tissue fibrosis. Furthermore, we discuss potential roles of genes homologous to mammalian DDRs identified in flies, worms and sponges. We show that the structural organization of these DDR-related genes is highly conserved throughout evolution suggesting that invertebrate DDRs may also function as receptors for collagen. By highlighting current questions about these unusual collagen receptors, we hope to attract new research on DDRs from a variety of different fields. [Copyright &y& Elsevier]

Abstract: The extracellular matrix provides a framework for cell adhesion, supports cell movement, and serves to compartmentalize tissues into functional units. Fibronectin is a core component of many extracellular matrices where it regulates a variety of cell activities through direct interactions with cell surface integrin receptors. Fibronectin is synthesized by many adherent cells which then assemble it into a fibrillar network. The assembly process is integrin-dependent and fibronectin–integrin interactions initiate a step-wise process involving conformational activation of fibronectin outside and organization of the actin cytoskeleton inside. During assembly, fibronectin undergoes conformational changes that expose fibronectin-binding sites and promote intermolecular interactions needed for fibril formation. In this review, the main steps of fibronectin assembly are described and recent studies on fibronectin conformational changes are discussed. [Copyright &y& Elsevier]

A new study identifies the extracellular matrix (ECM) component, SPARC (secreted protein acidic, rich in cysteine), as a critical determinant of tumour burden in the APCmin/+ model of intestinal cancer. [ABSTRACT FROM AUTHOR]

The article focuses on the history of the study conducted by researcher Mary L. Stearns regarding the development and orientation of the intercellular fibers of connective tissue. It provides overview of the study in which Stearns has discovered the importance of cell as architects of extracellular matrix (ECM) synthesis and organization of connective tissue. It also mentions the evolution of the study since several scientists have expanded its findings.