scholarly journals The CCN family: a new stimulus package

2003 ◽  
Vol 178 (2) ◽  
pp. 169-175 ◽  
Author(s):  
DR Brigstock
Keyword(s):  
Clinical Endocrinology ◽  
Cell Types ◽  
Tissue Growth ◽  
Ccn Proteins ◽  
Ccn Family ◽  
Igf Binding Proteins ◽  
Igf Binding ◽  
Multiple Cell ◽  
Activate Cell ◽  
And Migration

The CCN family comprises cysteine-rich 61 (CYR61/CCN1), connective tIssue growth factor (CTGF/CCN2), nephroblastoma overexpressed (NOV/CCN3), and Wnt-induced secreted proteins-1 (WISP-1/CCN4), -2 (WISP-2/CCN5) and -3 (WISP-3/CCN6). These proteins stimulate mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. Many of these activities probably occur through the ability of CCN proteins to bind and activate cell surface integrins. Accumulating evidence supports a role for these factors in endocrine pathways and endocrine-related processes. To illustrate the broad role played by the CCN family in basic and clinical endocrinology, this Article highlights the relationship between CCN proteins and hormone action, skeletal growth, placental angiogenesis, IGF-binding proteins and diabetes-induced fibrosis.

scholarly journals Extracellular-Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Titanium Surface ◽  
Wound Closure ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Tissue Growth ◽  
Titanium Implants ◽  
The Body ◽  
High Concentrations ◽  
And Migration

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.

Role of non-TSH factors in thyroid cell growth

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S231-S237 ◽  
Author(s):  
Margaret C. Eggo ◽  
Laura K. Bachrach ◽  
Gerard N. Burrow
Keyword(s):  
Dna Synthesis ◽  
Binding Proteins ◽  
Growth Stimulation ◽  
Cell Types ◽  
Thyroid Cell ◽  
Igf Binding Proteins ◽  
Thyroid Cells ◽  
Tetradecanoyl Phorbol Acetate ◽  
Biologic Effects ◽  
Igf Binding

Abstract. The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.

scholarly journals IGF-binding protein-5: flexible player in the IGF system and effector on its own

2002 ◽  
Vol 172 (3) ◽  
pp. 423-440 ◽  
Author(s):  
MR Schneider ◽  
E Wolf ◽  
A Hoeflich ◽  
H Lahm
Keyword(s):  
Biological Activities ◽  
Decisive Role ◽  
Cell Types ◽  
Recent Experimental Data ◽  
Igf Binding Proteins ◽  
Physiological Processes ◽  
Igf Binding ◽  
Membrane Bound ◽  
Available Information ◽  
Igf Binding Protein

The multiple activities of IGF-I and -II are modulated by a family of IGF-binding proteins (IGFBP-1 to -6). Although structurally related, each IGFBP has unique properties and exerts specific functions. IGFBP-5 is the most conserved IGFBP across species and was identified as an essential regulator of physiological processes in bone, kidney and mammary gland. In addition, IGFBP-5 appears to play a decisive role in the control of proliferation of specific tumour cell types. In many situations IGFBP5 exerts biological activities in the absence of IGFs, indicating the existence of IGF-independent actions. This concept was supported by the unexpected localisation of IGFBP-5 in the nucleus and the description of IGFBP-5-specific membrane-bound IGFBP-5 receptor(s). The scope of this review is to summarise the available information about the structure of IGFBP-5 and the regulation of its expression. Furthermore, the potential significance of IGFBP-5 in the regulation of physiological processes will be critically analysed in the light of recent experimental data.

scholarly journals Fibronectin Promotes Survival and Migration of Primary Neural Stem Cells Transplanted into the Traumatically Injured Mouse Brain

2002 ◽  
Vol 11 (3) ◽  
pp. 283-295 ◽  
Author(s):  
Matthew C. Tate ◽  
Deborah A. Shear ◽  
Stuart W. Hoffman ◽  
Donald G. Stein ◽  
David R. Archer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cellular Therapy ◽  
Cell Types ◽  
Survival Times ◽  
Germinal Zone ◽  
Cortical Contusion ◽  
Multiple Cell ◽  
And Migration

Multipotential stem cells are an attractive choice for cell therapy after traumatic brain injury (TBI), as replacement of multiple cell types may be required for functional recovery. In the present study, neural stem cells (NSCs) derived from the germinal zone of E14.5 GFP-expressing mouse brains were cultured as neurospheres in FGF2-enhanced medium. When FGF2 was removed in vitro, NSCs expressed phenotypic markers for neurons, astrocytes, and oligodendrocytes and exhibited migratory behavior in the presence of adsorbed fibronectin (FN). NSCs (105 cells) were transplanted into mouse brains 1 week after a unilateral, controlled, cortical contusion (depth = 1 mm, velocity = 6 m/s, duration = 150 ms) (n = 19). NSCs were injected either directly into the injury cavity with or without an injectable FN-based scaffold [collagen I (CnI)/ FN gel; n = 14] or into the striatum below the injury cavity (n = 5). At all time points examined (1 week to 3 months posttransplant), GFP+ cells were confined to the ipsilateral host brain tissue. At 1 week, cells injected into the injury cavity lined the injury penumbra while cells inserted directly into the striatum remained in or around the needle track. Striatal transplants had a lower number of surviving GFP+ cells relative to cavity injections at the 1 week time point (p < 0.01). At the longer survival times (3 weeks–3 months), 63–76% of transplanted cells migrated into the fimbria hippocampus regardless of injection site, perhaps due to cues from the degenerating hippocampus. Furthermore, cells injected into the cavity within a FN-containing matrix showed increased survival and migration at 3 weeks (p < 0.05 for both) relative to injections of cells alone. These results suggest that FGF2-responsive NSCs present a promising approach for cellular therapy following trauma and that the transplant location and environment may play an important role in graft survival and integration.

scholarly journals Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems

2003 ◽  
Vol 24 (6) ◽  
pp. 737-764 ◽  
Author(s):  
Stephanie R. Edmondson ◽  
Susan P. Thumiger ◽  
George A. Werther ◽  
Christopher J. Wraight
Keyword(s):  
Growth Factor ◽  
Normal Skin ◽  
The Body ◽  
Igf Binding Proteins ◽  
Endocrine Activity ◽  
Igf I ◽  
Igf Binding ◽  
Epidermal Homeostasis ◽  
Health And Disease ◽  
And Migration

Abstract GH and IGF-I and -II were first identified by their endocrine activity. Specifically, IGF-I was found to mediate the linear growth-promoting actions of GH. It is now evident that these two growth factor systems also exert widespread activity throughout the body and that their actions are not always interconnected. The literature highlights the importance of the GH and IGF systems in normal skin homeostasis, including dermal/epidermal cross-talk. GH activity, sometimes mediated via IGF-I, is primarily evident in the dermis, particularly affecting collagen synthesis. In contrast, IGF action is an important feature of the dermal and epidermal compartments, predominantly enhancing cell proliferation, survival, and migration. The locally expressed IGF binding proteins play significant and complex roles, primarily via modulation of IGF actions. Disturbances in GH and IGF signaling pathways are implicated in the pathophysiology of several skin perturbations, particularly those exhibiting epidermal hyperplasia (e.g., psoriasis, carcinomas). Additionally, many studies emphasize the potential use of both growth factors in the treatment of skin wounds; for example, burn patients. This overview concerns the role and mechanisms of action of the GH and IGF systems in skin and maintenance of epidermal integrity in both health and disease.

scholarly journals The Aminoterminal Insulin-Like Growth Factor (IGF) Binding Domain of IGF Binding Protein-3 Cannot Be Functionally Substituted by the Structurally Homologous Domain of CCN3

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5268-5274 ◽  
Author(s):  
Xiaolang Yan ◽  
Robert C. Baxter ◽  
Bernard Perbal ◽  
Sue M. Firth
Keyword(s):  
Growth Factor ◽  
Binding Site ◽  
Tissue Growth ◽  
Ccn Proteins ◽  
Homologous Proteins ◽  
Direct Role ◽  
High Affinity ◽  
Igf Binding ◽  
Related Proteins ◽  
Igfbp 3

IGF binding proteins (IGFBPs) are a family of structurally homologous proteins that bind IGFs with high affinities and can modulate IGF activity. The IGF binding site has been shown to comprise residues in both the aminoterminal and carboxyterminal domains. In recent years several proteins including members of the CCN (connective tissue growth factor, Cyr61, and nephroblastoma overexpressed) family were recognized as having structural homology in their aminoterminal domains to the IGFBPs. Despite their low or undetectable IGF binding ability, a proposal was made to rename them as IGFBP-related proteins. To test whether the aminoterminal domain of a CCN protein can fulfill the high-affinity IGF binding function of an IGFBP, we created a chimera in which the aminoterminal domain of IGFBP-3 was substituted with the aminoterminal domain of CCN3 (previously known as Nov). The CCN3-IGFBP-3 chimera bound IGFs and inhibited IGF activity very weakly, similar to CCN3 itself. Although structurally similar, the aminoterminal domain of CCN3 is unable to replace the aminoterminal domain of IGFBP-3 in forming a high-affinity IGF-binding site. These results argue against a direct role of CCN3 in the regulation of IGF bioavailability and indicate that the nomenclature of IGFBP-related proteins (which implies functional relationship to the classical IGFBPs) is inappropriate for CCN proteins.

scholarly journals Keratinocyte Function in Normal and Diabetic Wounds and Modulation by FOXO1

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yulan Wang ◽  
Dana T. Graves
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Transforming Growth Factor ◽  
Negative Impact ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Tissue Growth ◽  
Complex Interactions ◽  
Multiple Cell

Diabetes has a significant and negative impact on wound healing, which involves complex interactions between multiple cell types. Keratinocytes play a crucial role in the healing process by rapidly covering dermal and mucosal wound surfaces to reestablish an epithelial barrier with the outside environment. Keratinocytes produce multiple factors to promote reepithelialization and produce factors that enhance connective tissue repair through the elaboration of mediators that stimulate angiogenesis and production of connective tissue matrix. Among the factors that keratinocytes produce to aid healing are transforming growth factor-β (TGF-β), vascular endothelial growth factor-A (VEGF-A), connective tissue growth factor (CTGF), and antioxidants. In a diabetic environment, this program is disrupted, and keratinocytes fail to produce growth factors and instead switch to a program that is detrimental to healing. Changes in keratinocyte behavior have been linked to high glucose and advanced glycation end products that alter the activities of the transcription factor, FOXO1. This review examines reepithelialization and factors produced by keratinocytes that upregulate connective tissue healing and angiogenesis and how they are altered by diabetes.

scholarly journals Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

2021 ◽  
Vol 22 (10) ◽  
pp. 5234
Author(s):  
Daniela L. Rebolledo ◽  
María José Acuña ◽  
Enrique Brandan
Keyword(s):  
Skeletal Muscle ◽  
Tissue Growth ◽  
Muscle Physiology ◽  
Ccn Proteins ◽  
Matricellular Proteins ◽  
Ccn Family ◽  
Kinin System ◽  
Muscle Fibrosis ◽  
Vasoactive Peptides ◽  
Skeletal Muscle Fibrosis

The Cellular Communication Network (CCN) family of matricellular proteins comprises six proteins that share conserved structural features and play numerous biological roles. These proteins can interact with several receptors or soluble proteins, regulating cell signaling pathways in various tissues under physiological and pathological conditions. In the skeletal muscle of mammals, most of the six CCN family members are expressed during embryonic development or in adulthood. Their roles during the adult stage are related to the regulation of muscle mass and regeneration, maintaining vascularization, and the modulation of skeletal muscle fibrosis. This work reviews the CCNs proteins’ role in skeletal muscle physiology and disease, focusing on skeletal muscle fibrosis and its regulation by Connective Tissue Growth factor (CCN2/CTGF). Furthermore, we review evidence on the modulation of fibrosis and CCN2/CTGF by the renin-angiotensin system and the kallikrein-kinin system of vasoactive peptides.

scholarly journals Potential Role of CCN Proteins in Breast Cancer: Therapeutic Advances and Perspectives

2021 ◽  
Vol 28 (6) ◽  
pp. 4972-4985
Author(s):  
Kazi Ahsan Ahmed ◽  
Tasnin Al Hasib ◽  
Shamrat Kumar Paul ◽  
Md. Saddam ◽  
Afsana Mimi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multiple Roles ◽  
Matricellular Protein ◽  
Ccn Proteins ◽  
Biological Interactions ◽  
Ccn Family ◽  
Dual Nature ◽  
Functional Activities ◽  
And Migration

CCNs are a specific type of matricellular protein, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members, which exist only in vertebrates. The architecture of CCN proteins is multi-modular comprising four distinct modules. CCN Proteins achieve their primary functional activities by binding with several integrin7 receptors. The CCN family has been linked to cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, chondrogenesis, and wound healing, among other biological interactions. Breast cancer is the most commonly diagnosed cancer worldwide and CCN regulated breast cancer stands at the top. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. The pro-tumorigenic CCN1, CCN2, CCN3, and CCN4 may lead to human breast cancer, although the anti-tumorigenic actions of CCN5 and CCN6 are also present. Several studies have been conducted on CCN proteins and cancer in recent years. CCN1 and CCN3 have been shown to exhibit a dual nature of tumor inhibition and tumor suppression to some extent in quiet recent time. Pharmacological advances in treating breast cancer by targeting CCN proteins are also reported. In our study, we intend to provide an overview of these research works while keeping breast cancer in focus. This information may facilitate early diagnosis, early prognosis and the development of new therapeutic strategies.

Sign in / Sign up

Export Citation Format

Share Document