scholarly journals Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis

2021 ◽  
Vol 22 (9) ◽  
pp. 4340
Author(s):  
Iona J. MacDonald ◽  
Chien-Chung Huang ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Chih-Hsin Tang
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Evidence Base ◽  
Ccn Proteins ◽  
Matricellular Proteins ◽  
Substantial Evidence ◽  
Ccn Family ◽  
Cellular Processes

The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.

scholarly journals The Emerging Roles of CCN3 Protein in Immune-Related Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Linan Peng ◽  
Yingying Wei ◽  
Yijia Shao ◽  
Yi Li ◽  
Na Liu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Systemic Sclerosis ◽  
Structure And Function ◽  
Secreted Proteins ◽  
Ccn Proteins ◽  
Biological Functions ◽  
Ccn Family ◽  
Cellular Processes ◽  
Associated Proteins ◽  
And Function

The CCN proteins are a family of extracellular matrix- (ECM-) associated proteins which currently consist of six secreted proteins (CCN1-6). CCN3 protein, also known as nephroblastoma overexpressed protein (NOV), is a member of the CCN family with multiple biological functions, implicated in major cellular processes such as cell growth, migration, and differentiation. Recently, CCN3 has emerged as a critical regulator in a variety of diseases, including immune-related diseases, including rheumatology arthritis, osteoarthritis, and systemic sclerosis. In this review, we will briefly introduce the structure and function of the CCN3 protein and summarize the roles of CCN3 in immune-related diseases, which is essential to understand the functions of the CCN3 in immune-related diseases.

scholarly journals LncRNA XIST promotes extracellular matrix synthesis, proliferation and migration by targeting miR-29b-3p/COL1A1 in human skin fibroblasts after thermal injury

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Wei Cao ◽  
Youping Feng
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Western Blot ◽  
Thermal Injury ◽  
Human Skin Fibroblasts ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Long noncoding RNAs (lncRNAs) have been reported to be associated with dermis process during burn wound healing. This study aimed to investigate the role of lncRNA X-inactive specific transcript (XIST) in human skin fibroblasts (HSF) and extracellular matrix (ECM) as well as the regulatory network of XIST/microRNA-29b-3p (miR-29b-3p)/collagen 1 alpha 1 (COL1A1). Methods The wound samples were collected from 25 patients with deep partial thickness burn at day 5 after burn. The thermal injured model was established using HSF cells. The expressions of XIST, miR-29b-3p and COL1A1 were measured by quantitative real-time polymerase chain reaction and western blot. ECM synthesis, cell proliferation and migration were detected by western blot, cell counting kit-8 and trans-well assays, respectively. The interaction between miR-29b-3p and XIST or COL1A1 was explored by bioinformatics analysis and luciferase reporter assay. Results The expressions of XIST and COL1A1 were enhanced but miR-29b-3p expression was decreased after thermal injury. XIST overexpression promoted ECM synthesis, cell proliferation and migration in thermal injured HSF cells. However, XIST knockdown played an opposite effect. miR-29b-3p overexpression inhibited ECM synthesis, cell proliferation and migration, which was reversed by XIST. COL1A1 silence suppressed ECM synthesis, cell proliferation and migration by miR-29b-3p targeting. Moreover, COL1A1 up-regulation weakened the effect of XIST silence on ECM synthesis and HSF cell function. Conclusion XIST promoted ECM synthesis, cell proliferation and migration by sponging miR-29b-3p and targeting COL1A1 in HSF cells after thermal injury, indicating the promoting role of XIST in wound healing.

scholarly journals Leucocyte-Rich Platelet-Rich Plasma Enhances Fibroblast and Extracellular Matrix Activity: Implications in Wound Healing

2020 ◽  
Vol 21 (18) ◽  
pp. 6519
Author(s):  
Jeannie Devereaux ◽  
Narges Dargahi ◽  
Sarah Fraser ◽  
Kulmira Nurgali ◽  
Dimitrios Kiatos ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
Autologous Blood ◽  
Human Fibroblasts ◽  
White Blood Cells ◽  
High Concentration ◽  
Gene Expressions

Background: Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of platelets and leucocytes, which are fundamental fibroblast proliferation agents. Literature has emerged that offers contradictory findings about leucocytes within PRP. Herein, we elucidated the effects of highly concentrated leucocytes and platelets on human fibroblasts. Methods: Leucocyte-rich, PRP (LR-PRP) and leucocyte-poor, platelet-poor plasma (LP-PPP) were compared to identify their effects on human fibroblasts, including cell proliferation, wound healing and extracellular matrix and adhesion molecule gene expressions. Results: The LR-PRP exhibited 1422.00 ± 317.21 × 103 platelets/µL and 16.36 ± 2.08 × 103 white blood cells/µL whilst the LP-PPP demonstrated lower concentrations of 55.33 ± 10.13 × 103 platelets/µL and 0.8 ± 0.02 × 103 white blood cells/µL. LR-PRP enhanced fibroblast cell proliferation and cell migration, and demonstrated either upregulation or down-regulation gene expression profile of the extracellular matrix and adhesion molecules. Conclusion: LR-PRP has a continuous stimulatory anabolic and ergogenic effect on human fibroblast cells.

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 Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression

2018 ◽  
Vol 19 (11) ◽  
pp. 3300 ◽  
Author(s):  
Heydi Noriega-Guerra ◽  
Vanessa Freitas
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cell Communication ◽  
Dynamic Network ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Matricellular Proteins ◽  
Cellular Processes

The extracellular matrix (ECM) is a crucial component of the tumor microenvironment involved in numerous cellular processes that contribute to cancer progression. It is acknowledged that tumor–stromal cell communication is driven by a complex and dynamic network of cytokines, growth factors and proteases. Thus, the ECM works as a reservoir for bioactive molecules that modulate tumor cell behavior. The hepatocyte growth factor (HGF) produced by tumor and stromal cells acts as a multifunctional cytokine and activates the c-MET receptor, which is expressed in different tumor cell types. The HGF/c-MET signaling pathway is associated with several cellular processes, such as proliferation, survival, motility, angiogenesis, invasion and metastasis. Moreover, c-MET activation can be promoted by several ECM components, including proteoglycans and glycoproteins that act as bridging molecules and/or signal co-receptors. In contrast, c-MET activation can be inhibited by proteoglycans, matricellular proteins and/or proteases that bind and sequester HGF away from the cell surface. Therefore, understanding the effects of ECM components on HGF and c-MET may provide opportunities for novel therapeutic strategies. Here, we give a short overview of how certain ECM components regulate the distribution and activation of HGF and c-MET.

scholarly journals The Aspects of CCN Protein Family on Breast Cancer

2021 ◽  
Author(s):  
Abu Saim Mohammad Saikat ◽  
Kazi Ahsan Ahmed ◽  
Md. Saddam ◽  
Afsana Mimi ◽  
Tasnin Al Hasib ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Protein Family ◽  
Ccn Proteins ◽  
Biological Interactions ◽  
Immune Functions ◽  
Matricellular Proteins ◽  
Ccn Family ◽  
Aberrant Expression ◽  
And Migration

CCNs are specific type of matricellular proteins, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members in mammals. The architecture of CCN proteins is multimodular and comprises four distinct motifs. CCN proteins achieve their specific physiological functions by binding to integrin receptors. The CCN family has been implicated in both cure and disease with impacts on biological interactions, such as cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, immune functions, chondrogenesis, and wound healing. Breast cancer is the most commonly diagnosed cancer worldwide and the leading cause of cancer mortality among women triggered by atypical expression of CCNs. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. Aberrant expression of CCN1 intensifies the proliferation of epithelial cells that line the lobes and ducts of the breast. Evidence also shows that the expression of CCN2 can ameliorate tumor growth and metastasis. However, CCN3 (NOV), CCN5 (WISP-2), and CCN6 (WISP-3) are consistent with neoplastic development and metastasis repression. Particular CCN members can develop tumors and cancer progression, whereas others can competitively counter the processes. Several studies have been conducted on CCN proteins and cancer in recent years. In our study, we intend to provide an overview of those research works while keeping breast carcinoma on focus. We believe that the importance of the CCN protein family in breast cancer should be reconsidered.

scholarly journals CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology

2021 ◽  
Author(s):  
Veronica Giusti ◽  
Katia Scotlandi
Keyword(s):  
Musculoskeletal System ◽  
Adult Life ◽  
Current Understanding ◽  
Minor Role ◽  
Ccn Proteins ◽  
Matricellular Proteins ◽  
Ccn Family ◽  
Surface Receptors ◽  
Cell Commitment ◽  
A Minor

AbstractThe acronym for the CCN family was recently revised to represent “cellular communication network”. These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN proteins in mesenchymal stem cell commitment and a pivotal role for CCN1, CCN2 and their alter ego CCN3 in chondrogenesis and osteogenesis; CCN4 plays a minor role and the role of CCN5 and CCN6 is still unclear. CCN proteins also participate in osteoclastogenesis and myogenesis. In adult life, CCN proteins serve as mechanosensory proteins in the musculoskeletal system providing a steady response to environmental stimuli and participating in fracture healing. Substantial evidence also supports the involvement of CCN proteins in inflammatory pathologies, such as osteoarthritis and rheumatoid arthritis, as well as in cancers affecting the musculoskeletal system and bone metastasis. These matricellular proteins indeed show involvement in inflammation and cancer, thus representing intriguing therapeutic targets. This review discusses the current understanding of CCN proteins in the musculoskeletal system as well as the controversies and challenges associated with their multiple and complex roles, and it aims to link the dispersed knowledge in an effort to stimulate and guide readers to an area that the writers consider to have significant impact and relevant potentialities.

The Roles of a Matricellular CCN Family Protein CCN5 in Cardiac Fibrosis of Heart Failure

Nano LIFE ◽  
2019 ◽  
Vol 09 (03) ◽  
pp. 1941003
Author(s):  
Jie Liu ◽  
Tao Zhuang ◽  
Xiaoli Chen ◽  
Lin Zhang ◽  
Yuzhen Zhang
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Cardiac Fibrosis ◽  
Severe Heart Failure ◽  
Matricellular Protein ◽  
Ccn Proteins ◽  
Post Injury ◽  
Ccn Family ◽  
Nonstructural Components ◽  
Major Player

Cardiac fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease and a post-injury response that drives progression to heart failure. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, such as angiotensin II, TGF-[Formula: see text] and endothelin-1, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Matricellular CCN proteins spatiotemporally regulated nonstructural components of the extracellular matrix (ECM) and participated in many essential biological functions, including wound healing and fibrotic diseases. CCN5 exhibited the opposing effects of CCN2 on the development of cardiac hypertrophy and fibrosis, and overexpression of matricellular protein CCN5 in the heart by adenoviral deliver significantly improved cardiac fibrosis in severe heart failure. Future time- and cell-specific study of CCN5 effect and its domain-specific function on fibrotic development and progression will advance our understanding of cardiac fibrosis, and meanwhile provide opportunities for therapeutic intervention of heart failure.

scholarly journals A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Brandon J. Rose ◽  
David L. Kooyman
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Embryonic Development ◽  
Tissue Remodeling ◽  
Matrix Metalloproteases ◽  
Extracellular Matrix Molecules ◽  
Cartilage Biology

Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases. The purpose of this review is to discuss matrix metalloproteinases as they pertain to cartilage health, both under physiological circumstances and in the instances of osteoarthritis and rheumatoid arthritis, and to discuss their utility as biomarkers in instances of the latter.

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