Perbal / Takigawa CCN proteins in health and disease

An overview of the Fifth International Workshop on the CCN family of genes
1. Auflage 2010
ISBN: 978-90-481-3779-4
Verlag: Springer Netherland
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 338 Seiten, eBook

The CCN family of genes currently comprises six secreted proteins (designated CCN16 i.e., Cyr61/CCN1; ctgf/CCN2; Nov/CCN3; WISP1/CCN4; WISP2/CCN5, and WISP3/CCN6) showing a strikingly conserved primary structure, with four modules sharing partial identity with IGF binding proteins, Von Willebrand protein, thrombospondin and several matricellular proteins and growth factors. The current view is that CCN proteins modulate signaling pathways that involve regulatory components of the extracellular matrix. As such, they likely act as a central hub in the regulation of mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types.The 5th international workshop on the CCN family of genes, that was held in Toronto in 2008 brought together scientists from around the world who have an interest in the biological roles of this emerging family of proteins. On an educational point of view, the workshop was a unique place for an efficient diffusion of scientific information. The present book comprises a series of selected manuscripts that are based on the original communications that were presented at the meeting by worldwide leaders in the field of CCN biology. All major aspects of CCN proteins biology in both normal and pathological conditions are covered in this volume, from structure-functions analysis up to the involvement of CCN proteins in complex physiological functions. In addition to reports that support the Yin-Yang concept of CCN proteins driving opposite effects on the same biological process, this book also comprises several contributions that point to CCN proteins as amenable targets for therapeutic manipulation of disease processes.Together with the special issue of Journal of Cell Communication and Signaling in which authors have extended on the original data presented at the meeting, the present Proceedings provide an instant picture and unique update of the state of the art in the CCN field.

Zielgruppe

Research

Autoren/Hrsg.

Perbal, Annick

Takigawa, Masaharu

Perbal, Bernard

Inhaltsverzeichnis

A Recent Breakthrough in the CCN Field: Functional Interactions Between CCN2 and CCN3 are Uncovered.- Report on the Fifth International Workshop on the CCN Family of Genes.- Asking the Right Questions: What Can the Structure of the CCN Protein Domains Tell Us?.- Nucleophosmin/B23: A Multifunctional Regulator that Determines the Fate of CCN2 mRNA.- The CCN Genes as the “Master” Regulators of Angiogenesis, Vasculogenesis, Fibrogenesis and Cell Differentiation/Fate Specification in Mechanical Force-Driven Developmental Processes and Pathological Events.- A Monoclonal Antibody Approach to CCN5 Domain Analysis.- Matricellular Protein CCN2 Produced by Tubular Epithelial Cells Plays a Pivotal Role in Renal Fibrogenesis.- Cooperative Regulation of Cell Proliferation and Differentiation by CCN2 and CCN3.- The Role of CCN3 in Mesenchymal Stem Cells.- Role of Connective Tissue Growth Factor in Cardiac Fibrosis.- Gene Expression of CCN Family Members in Young and Aged Human Skin In Vivo.- Global Expression Profiling Reveals a Role for CTGF/CCN2 in Lactogenic Differentiation of Mouse Mammary Epithelial Cells.- CCN3 (NOV): A Negative Regulator of CCN2 (CTGF) Activity and an Endogenous Inhibitor of Fibrosis in Experimental Diabetic Nephropathy.- Inhibitors of Connective Tissue Growth Factor (CCN2)-Mediated Fibrogenesis: Underlying Mechanisms and Prospects for Anti-fibrotic Therapy.- CCN3 Promotes Melanoma Progression by Regulating Integrin Expression, Adhesion and Apoptosis Induced by Cytotoxic Drugs.- CCN3: A NOVel Growth Factor in Leukaemia.- Prognostic Relevance of CCN3 in Bone Sarcomas.- CCN6 Regulates Breast Cancer Growth and Invasion Through Modulation of IGF Signaling and Epithelial to Mesenchymal Transition.- Novel Transcriptional Regulation of CCN2/CTGF by NuclearTranslocation of MMP3.

Leseproben

"Chapter 2 Report on the Fifth InternationalWorkshop on the CCN Family of Genes (p. 5-6)

A. E. Irvine, B. Perbal, and H. Yeger

Abstract The Fifth International Workshop on the CCN Family of Genes was held in October 2008. This bi-annual meeting provides a unique forum for researchers in the CCN field to present and exchange ideas. The CCN family of regulatory proteins play key roles in both normal cell development and a wide range of pathologies. This was reflected in the breadth of basic cell biology and translational studies presented at the conference. Exciting new in vitro and in vivo model systems are providing new insights into the functional complexity of the CCN family and promise much more to come.

Keywords CCN1 · CCN2 · CCN3 · CCN4 · CCN5 · CCN6 · Cyr61 · CTGF · NOV · Wisp-1 · Wisp-2 · Wisp-3

The Fifth InternationalWorkshop on the CCN Family of Genes was held in Toronto, October 18–22, 2008. The meeting was organised by Herman Yeger, Bernard and Annick Perbal and provided an excellent environment for discussion and interaction amongst a diverse and enthusiastic group of researchers. The Journal of Communication and Cell Signalling has now been launched as the official journal of the International CCN Society.

The publishers, Springer Science & Business Media, sponsored the opening plenary session of the conference and also three scholarships for young investigators to attend the meeting. The first Springer Award for outstanding research in this field was presented by Peter Butler (Springer) to Professor Paul Bornstein by for his work on matricellular proteins. Professor Bornstein gave a stimulating talk focussed on the concept of ‘dynamic reciprocity’ and presented his studies using thrombospondin (TSP-1 and TSP-2) null mice. Opening remarks by Professor Perbal coupled with Professor Bornstein’s lecture set the stage nicely for the meeting to follow. The first session of the meeting on CCN Structure/Function and Expression opened with a presentation by Dr. Ravi Acharya (Bath, England).

Dr. Acharya examined the protein structure of the CCN family and discussed how this might contribute to the functional differences between family members. By modelling the three dimensional structure of the domains he provided insight as to how this might influence interaction with other key molecules. This was followed by a series of presentations on CCN2 gene regulation lead by Dr. Satoshi Kubota (Okayama, Japan) who described the characterisation of Nucleophosmin/B23 as a regulator of CCN2 in chicken chondrocytes. Nucleophosmin has the ability to shuttle between the nucleus and the cytoplasm and Satoshi presented extensive experiments demonstrating both transcriptional (nuclear) and post-transcriptional (cytoplasmic) regulation of CCN2.

Further work from this group, presented by Dr. Ogawara, demonstrated that mi-RNA 18a acts on CCN2 via the 3-UTR and regulates human chondrocytic differentiation. This work now introduces a new level of CCN regulation that should get increasing attention. In a change of cellular context, Dr. Cabello-Verrugio (Santiago, Chile) presented work on the regulation of CCN2 by TGF-b and LPA in skeletal muscle cells in parallel with other studies from his lab suggesting dependency on decorin and involvement of the endocytic receptor LRP-1. He used the C2C12 myoblast cell line to show a dose-dependent induction of CCN2 where the induction is mediated classically through TGFbR1 and SMAD2/3."