International Review of Cytology (eBook)

A Survey of Cell Biology

Kwang W. Jeon (Herausgeber)

eBook Download: PDF | EPUB

2007 | 1. Auflage
272 Seiten
Elsevier Science (Verlag)
978-0-08-047115-0 (ISBN)

Infos

International Review of Cytology presents current advances and comprehensive reviews in cell biology - both plant and animal. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.

Inhalt

Front Cover 1
A Survey of Cell Biology 4
Copyright Page 5
Contents 6
Contributors 10
Chapter 1: Role of CCN2/CTGF/Hcs24 in Bone Growth 12
I. Introduction 13
II. The CCN Family 13
A. General Structure and Terminology 13
B. Members of the CCN Family 15
III. CCN2: A Multiple Regulator of Mesenchymal Tissue Development 19
A. Distribution in Normal Tissues 19
B. Physiological Roles in Connective Tissues 20
C. Involvement in Wound Healing 21
D. CCN2 and Fibrotic Disorders: A Pathological Role 21
E. Malignant Phenotypes and CCN2 in Tumors 22
IV. CCN2 and Bone Cell Biology 23
A. Structure and Evolution of Bone and CCN2 23
B. Roles of CCN2 in Bone Cell Biology 26
C. Regulation of ccn2 Gene Expression 34
D. Utility of CCN2 in Regenerative Therapy of Bone 39
V. Concluding Remarks 41
Acknowledgments 42
References 42
Chapter 2: Action Potential in Charophytes 54
I. Introduction 54
A. Defining Features of the Action Potential 54
B. Why Is the Study of Charophyte AP Important 60
II. Historical Background (Up to Late 1990s) 60
A. Experimental Techniques 60
B. The Stimulus 64
C. Coupling to Streaming Stoppage 65
D. Resolving Responses at Plasmalemma and Tonoplast 66
E. Resolving Individual Transporters 68
F. Manipulating Inside and Outside Media 74
G. Effect of Temperature 78
H. Signal Propagation 78
I. Capacitance at the Time of Excitation 79
J. Early Models 79
III. New Approaches in the New Century 82
A. IP3 (Inositol 1,4,5, -triphosphate) and Ca2+ from Internal Stores 82
B. Involvement of AP in Wound Signaling 84
C. AP and Turgor Regulation 84
IV. Summary 85
Acknowledgments 87
References 87
Chapter 3: Similarity of the Domain Structure of Proteins as a Basis for the Conservation of Meiosis 94
I. Introduction 95
II. Homomorphism of Cytological Features of Meiosis 97
III. Functional Analogy of Morphogenetic Proteins in Meiosis 100
A. Ultrastructure of Synaptonemal Complexes 101
B. Proteins of the SC Central Space 104
C. Proteins of SC Lateral Elements 116
D. Evolutionary Mystery of SC Proteins 119
IV. Recombination Enzymes 120
A. Recombination Nodules as Compartments for Recombination Enzymes 120
B. RecA-Rad51 Protein Family 122
V. Proteins of the SMC Family 125
A. SMC and Cohesin Proteins in Meiosis 127
B. Protein Shugoshin Ensures Sister Chromatid Nondisjunction in Meiosis I 132
VI. Importance of Secondary Protein Structure for Ultrastructure Morphogenesis 133
A. Kinetochore Proteins 134
B. Connexins and Innexins (Pannexins) 135
C. Nuclear Pore Proteins 137
VII. Conclusion: Organelle Morphology as Dependent on the Protein Structure 141
References 143
Chapter 4: Fibroblast Differentiation in Wound Healing and Fibrosis 154
I. Introduction 155
II. Inflammation and Wound Healing 155
A. Inflammation 155
B. Wound Healing 156
C. Healing versus Scarring 158
D. Distinction Between Healing and Scarring 158
E. Cellular Basis of Healing and Scarring 159
III. Fibroblasts and Myofibroblasts 159
A. Fibroblasts 159
B. Myofibroblasts 160
C. Origin of the Fibroblast 165
D. Origin of the Myofibroblast 167
IV. Fibrogenic Mediators 168
A. Fibrogenic Mediators 168
B. Signal Transduction in Fibroblasts 171
C. Fibroblast Responses 173
V. Regulation of Fibrogenesis 177
A. Resolution or Progression 177
B. Remodeling 179
C. Therapies Aimed at Downregulating Fibroblast Function 180
VI. Concluding Remarks 181
References 181
Chapter 5: Tumor Hypoxia and Targeted Gene Therapy 192
I. Introduction 192
A. Tumor Hypoxia 192
B. Cellular Signaling in Response to Hypoxia 193
II. Hypoxia-Targeted Gene Therapy 195
A. Therapeutic Modification of the Hypoxic Signaling 196
B. Hypoxia-Regulated Therapeutic Gene Expression 199
C. Hypoxia-Targeted Gene Therapy Vectors 200
III. Combination of Hypoxia Gene Therapy with Conventional Treatments 207
A. Hypoxia Gene Therapy and Radiotherapy 207
B. Hypoxia Gene Therapy and Chemotherapy 210
IV. Concluding Remarks 212
References 212
Chapter 6: Cellular Basis of Chronic Obstructive Pulmonary Disease in Horses 224
I. Introduction 225
II. Morpho-Functional Features of Horse Lungs 227
A. Morphology 227
B. Physiology 230
III. Cytological Features of Equine Lungs 232
IV. Chronic Obstructive Pulmonary Disease (COPD) in Horses 234
A. Etiology and Pathogenesis 234
B. Morphological Features of COPD 238
V. Conclusions and Perspectives 249
References 251
Index 260

Textauszug

Role of CCN2/CTGF/Hcs24 in Bone Growth

Satoshi Kubota; Masaharu Takigawa* [e-mail]    Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
* Corresponding author. E‐mail address:

Abstract

Our bones mostly develop through a process called endochondral ossification. This process is initiated in the cartilage prototype of each bone and continues through embryonic and postnatal development until the end of skeletal growth. Therefore, the central regulator of endochondral ossification is the director of body construction, which is, in other words, the determinant of skeletal size and shape. We suggest that CCN2/CTGF/Hcs24 (CCN2) is a molecule that conducts all of the procedures of endochondral ossification. CCN2, a member of the CCN family of novel modulator proteins, displays multiple functions by manipulating the local information network, using its conserved modules as an interface with a variety of other biomolecules. Under a precisely designed four‐dimensional genetic program, CCN2 is produced from a limited population of chondrocytes and acts on all of the mesenchymal cells inside the bone callus to promote the integrated growth of the bone. Furthermore, the utility of CCN2 as regenerative therapeutics against connective tissue disorders, such as bone and cartilage defects and osteoarthritis, has been suggested. Over the years, the pathological action of CCN2 has been suggested. Nevertheless, it can also be regarded as another aspect of the physiological and regenerative function of CCN2, which is discussed as well.

Key words

Bone growth

Endochondral ossification

Bone regeneration

CCN family

Cartilage/chondrocytes

Skeletal development

Connective tissue growth factor (CTGF)

I Introduction

In mammals, the development of most bones in the skeleton is initiated by the preparation of the cartilage prototype and is accomplished through endochondral ossification or its related process. Endochondral ossification occurs mainly by growth plate chondrocytes in a precisely organized architecture with four‐dimensional (i.e., temporal and spatial) polarity of cytodifferentiation, in collaboration with vascular endothelial cells and osteoblasts, which invade through the cartilage canal. This complex biological process is under the control of a vast number of systemic hormones and local growth factors. Analogous to a full orchestra that needs a conductor to play polyphonic music with multiple instruments, certain key molecules have to modulate the functioning status of these signaling molecules and integrate the extracellular information in a harmonized manner to maintain the proper biological architecture of the growth plate and to promote the endochondral ossification toward bone growth. We suggest that CCN2, which is a classical member of the CCN protein family and was formerly called the connective tissue growth factor (CTGF)/hypertrophic chondrocyte‐specific gene product 24 (Hcs24)/ecogenin, is one such conductor/modulator of bone growth.

The functional characteristics of CCN2 as a conductor/modulator are represented by the fact that CCN2 is capable of promoting both the growth and differentiation of most mesenchymal cells involved in endochondral ossification. This apparently contradictory functionality may explain how CCN2 acts as a central driver of cartilage/bone growth and regeneration. In this article, we first briefly introduce the novel family of modulator proteins, namely the CCN family. Thereafter, we summarize advances in CCN2 research, mainly from the viewpoint of the molecular and cellular biology of bone growth and regeneration.

II The CCN Family

A General Structure and Terminology

The acronym “CCN” does not represent any structural or functional aspect of this gene family, but is a simple assemblage of the three classical members recognized earlier. This “family name” was first given in 1993 by Bork from the first letters of Cyr61 (cysteine‐rich protein 61), CTGF (connective tissue growth factor), and NOV (nephroblastoma‐overexpressed gene). Thereafter, three additional members were newly classified in this family (Brigstock, 1999; Lau and Lam, 1999; Perbal, 2004; Perbal and Takigawa, 2005; Takigawa et al., 2003). During this emerging period, a number of different names were independently assigned to each member by different research groups, thereby resulting in significant confusion in terminology (Baxter et al., 1998; Grotendorst et al., 2000; Moussad and Brigstock, 2000). To resolve this problem, a unified nomenclature was proposed in 2003, in which each member was renamed numerically under the family name, CCN (Brigstock et al., 2003). The relevance between the unified and original name of each member is summarized in Fig. 1A. Mammals possess six members in their genome so far, and no evidence for another member has yet been described.

Fig. 1 The CCN family. (A) The six members identified in the mammalian genomes. Previous designations given to each gene member are shown in parentheses. The members are placed based on a genetic dendrogram previously proposed (Perbal and Takigawa, 2005). (B) General structure of the mRNA and the nascent protein of a CCN family member. The mRNA is the assemblage of five exons (top of the panel) with the 5′‐cap and 3′‐poly(A) tail structures. Exons (ex) 1, 2, 3, 4, and 5 encode the signal peptide for secretion (a crescent), insulin‐like growth factor‐binding protein module (IGFBP), thrombospondin type 1 repeat module (TSP1), von Willebrand factor type C repeat (VWC) module, and carboxyl terminal cysteine knot (CT) module, respectively, except for CCN5, which lacks the CT module. The open reading frame is flanked by the 5′‐untranslated region (UTR) and the 3′‐UTR, which are crucial for the posttranscriptional regulation of gene expression in most members.

Although the genomic organization of the members demonstrates remarkable variety, all of the gene products retain a highly characteristic structure. Except for CCN6, these proteins consist of four conserved protein modules connected in tandem in order, following an N‐terminal signal peptide for secretion. It should be noted that these four modules—insulin‐like growth factor binding protein (IGFBP), von Willebrand factor type C repeat (VWC), thrombospondin type 1 repeat (TSP1), and C‐terminal cysteine‐knot (CT) modules—contain conserved cysteine residues and are highly interactive with a variety of other molecules, thus providing a structural basis for the multiple functionality of CCN member proteins (Perbal and Takigawa, 2005). Interestingly, each module is encoded by the corresponding single exon, and the boundaries of exons in mRNA strictly correspond to the module boundary in protein (Fig. 1B). Therefore, the CCN members are supposed to have developed by exon shuffling along the course of evolution (Patthy, 1987). In this context, the conserved cysteine residues involved in all of the modules are supposed to determine the proper tertiary structure of each module by intramodular interactions rather than by intermodular/intermolecular interactions (Brigstock, 1999). In the mRNAs, the coding regions are flanked by 5′‐ and 3′‐untranslated regions (UTR) that contain critical regulatory elements of gene expression, which will be described later (Kubota and Takigawa, 2002).

B Members of the CCN Family

1 CCN1/Cyr61/Cef10

The first member of the CCN family was identified as one of the immediate‐early genes in mouse fibroblasts in 1989. Because of the 38 cysteine residues in the gene product, which is currently recognized to be conserved among all of the CCN family proteins, this gene was designated cysteine‐rich 61 (cyr61) (O'Brien et al., 1990; Simmons et al., 1989). Mammalian ccn1 genes are quite compact with relatively short introns, as observed in ccn2. In terms of protein structure, CCN1/Cyr61 is uniquely characterized by spacer/hinge amino acid stretches located between the VWC and TSP modules (Bork, 1993). However, the functional significance of this intermodular peptide is still unclear.

The CCN1 protein is known to mediate integrin‐associated cell adhesion events while promoting wound healing, angiogenesis, and chondrogenesis, as also observed in the case of CCN2 (Chen et al., 2001a,b; Jedsadayanmata et al., 1999; Kireeva et al., 1997; Schober et al., 2002). In addition, when we stimulated chondrocytic cells with different types of cytokines, ccn1 and ccn2 displayed a similar response to all the stimuli examined, thus indicating that they may be engaged in similar missions in the metabolism of skeletal tissues (Moritani et al., 2005). Nevertheless, a difference in their biological roles was also clearly represented by the phenotypic difference between knockout (KO) mice of ccn1 and ccn2. Most of ccn1 KO mice were reported to be embryonic lethal, due to a failure of embryonic vascular system development in placenta (Mo et...

Produkt-Details

• Erscheint lt. Verlag: 7.2.2007
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Histologie / Embryologie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-047115-3 / 0080471153
• ISBN-13: 978-0-08-047115-0 / 9780080471150