Special Issue "Extracellular Matrix Remodeling"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 15 December 2018

Special Issue Editor

Guest Editor
Prof. Nicoletta Gagliano

Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy
Website | E-Mail
Interests: tumor invasion; tendon biology; fibrosis; gingival overgrowth; epithelial-to-mesenchymal transition; collagen turnover; matrix metalloproteinases

Special Issue Information

Dear Colleagues,

The extracellular matrix (ECM) is where cells live. It is composed of collagen and elastic fibers, glycosaminoglycans and proteoglycans, and by several glycoproteins. In most tissues, fibril-forming collagen type I is the major constituent of ECM.

The function of the ECM goes beyond providing mechanical support to cells and tissues. In fact, cells are embedded into ECM and interact with its components through their surface receptors, such as integrins, so cell-ECM interaction plays a key role in influencing different cell activities such as cell proliferation and migration. Moreover, the ECM sequesters and releases growth factors affecting important cellular pathways. Overall, the ECM strongly influences and affects cell behavior and tissue homeostasis.

Cell-matrix and cell-cell interactions are modulated by matricellular proteins, such as SPARC, tenascin and thrombospondin, characterized as non-structural extracellular modulators of cellular functions. Their activity is primarily related to their de-adhesive properties, but they are also able to interact with intracellular compartments.

ECM is a highly dynamic structural network that continuously undergoes controlled remodeling mediated by matrix-degrading enzymes, the matrix metalloproteinases (MMPs) under normal conditions.

Quantitative and qualitative deregulation of ECM remodeling and, especially, of collagen turnover, is responsible of the alteration of ECM composition and structure, associated with the development and progression of several pathologic conditions. For example, organ fibrosis is determined by the abnormal accumulation of ECM components, and an increased ECM remodeling is observed in tumor invasion.

The understanding of the diverse biological roles and properties of the ECM components will be helpful to develop new therapeutic tools for disease treatment.

Prof. Nicoletta Gagliano
Guest Editor

Manuscript Submission Information

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  • fibrosis
  • tumor invasion
  • collagen turnover
  • matrix metalloproteinases
  • matricellular proteins
  • cell-extracellular matrix interaction

Published Papers (1 paper)

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Open AccessArticle Action of the Metalloproteinases in Gonadal Remodeling during Sex Reversal in the Sequential Hermaphroditism of the Teleostei Fish Synbranchus marmoratus (Synbranchiformes: Synbranchidae)
Received: 23 February 2018 / Revised: 14 April 2018 / Accepted: 19 April 2018 / Published: 24 April 2018
PDF Full-text (7669 KB) | HTML Full-text | XML Full-text | Supplementary Files
Teleostei present great plasticity regarding sex change. During sex reversal, the whole gonad including the germinal epithelium undergoes significant changes, remodeling, and neoformation. However, there is no information on the changes that occur within the interstitial compartment. Considering the lack of information, especially
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Teleostei present great plasticity regarding sex change. During sex reversal, the whole gonad including the germinal epithelium undergoes significant changes, remodeling, and neoformation. However, there is no information on the changes that occur within the interstitial compartment. Considering the lack of information, especially on the role played by metalloproteinases (MMPs) in fish gonadal remodeling, the aim of this study was to evaluate the action of MMPs on gonads of sex reversed females of Synbranchus marmoratus, a fresh water protogynic diandric fish. Gonads were processed for light microscopy and blood samples were used for the determination of plasma sex steroid levels. During sex reversal, degeneration of the ovaries occurred and were gradually replaced by the germinal tissue of the male. The action of the MMPs induces significant changes in the interstitial compartment, allowing the reorganization of germinal epithelium. Leydig cells also showed an important role in female to male reversion. The gonadal transition coincides with changes in circulating sex steroid levels throughout sex reversion. The action of the MMPs, in the gonadal remodeling, especially on the basement membrane, is essential for the establishment of a new functional germinal epithelium. Full article
(This article belongs to the Special Issue Extracellular Matrix Remodeling)

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Authors: Fernández A, Veloso P, Cárdenas A, Astorga J, Hernández M.
Affiliation: Laboratory of Periodontal Biology, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
Tentative title: Expression of Toll-like receptors 2 and 4 and matrix metalloproteinases in symptomatic and asymptomatic apical periodontitis.

Authors: Dr. Sonja E LOBO
Affiliation: Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil
Tentative title: The cellular interactions and crosstalks related to ECM remodeling in healthy and patological conditions

Authors: Maria Cristina d'Agostino 1, Elena Monica Borroni 2, Elisabetta Tibalt, Stefano Respizzi 1, Johannes Holfeld 4, Kenneth Craig S. Vincent 5, Fabio Grizzi 3
Affiliations: 1 ESWT Center, Rehabilitation Department, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy
2 Department of Medical Biotechnologies and Translational Medicine, University of Milan, Italy
3 Department of Immunology and Inflammation, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy
4 Department for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
5 Kompass Health Associate, Auckland (NZ) – Shockwave & Isokinetic Centre, Melbourne
Tentative title: Extracorporeal Shock Wave Therapy as Effector in Tissue Healing, Extra-Cellular Matrix Reversal and Immune Cell Network Dynamics
Abstract: The term “fibrosis” defines the abnormal deposition of extra-cellular matrix (ECM) made-up of a variety of collagenic and non-collagenic proteins, glycoproteins, proteoglycans, which together form a complex scaffold on which cells adhere, grow, and differentiate. ECM molecules are predominantly synthesized by activated fibroblasts. Maintenance of the normal structure and function of the ECM involves constant remodeling, which results from regulated, low levels of ECM synthesis and degradation. During wound healing, there is a short-lived shift in the balance of synthesis and degradation, which leads to a transient increase in collagen production and deposition. A continuous imbalance resulting in major alterations in both the quantity, composition and distribution pattern of the ECM causes fibrosis. Excessive accumulation represents a distinctive feature not only in “pathological” skin scars and in diseases such as scleroderma, osteogenesis imperfecta, and scurvy, but also in some other diseases of the lung, kidney and liver characterized by tissue fibrosis. Regardless of the possible heterogenous etiopathogenesis of fibrosis, it is recognized that activated fibroblasts bear receptors, that bind various growth factors and cytokine and that cells mediating innate or adaptive immunity produce the majority of cytokines and chemokines regulating its gene expression. Restoring of a normal structure and “tropism” of tissues and organs, both after trauma and in different diseases represents nowadays a great challenge for scientists, whose main efforts are aimed to Regenerative Medicine. From this point of view, although still under investigation, Extracorporeal Shock Wave Therapy (ESWT), represent nowadays a promising therapeutic tool: as a mechanical force, through mechano-transduction, it may act by positively regulating inflammation (i.e. probably as immunomodulator), to induce neo-angiogenesis and stem cells activities, thus improving tissue regeneration and healing. Here we explore and discuss the potential action of shock wave on the reversibility of the fibrotic process and the effects of mechanical actions on the dynamics of the immune microenvironment.

Authors: Niccolò Bitto 1, Eleonora Liguori 1, Vincenzo La Mura 1,2
Affiliations: 1 Internal Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Donato, Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, San Donato Milanese (MI), Italy.
2 A. M. and A. Migliavacca-Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Tentative title: Hepatic stellate cells, liver fibrosis and coagulation
Abstract: Fibrogenesis is a complex biochemical process that represents the hallmark of damage for the most common chronic diseases of the liver. The activation of Hepatic stellate cells (HSC) is the key pathogenic mechanism for the initiation, progression, and regression of liver fibrosis. During last years, several studies have gone more in depth on the complex and tightly regulated cross-talk at the level of hepatic microcirculation owing to sinusoidal endothelial cells (SEC), Kuppfer cells (KC), hepatocytes with HSC underling the importance of other cytotypes in fibrogenesis.
Our manuscript would offer an overview on the pathogenic role played by coagulation and thrombin generation in this complex cellular cross-talk by considering fibrosis a wound healing process secondary to micro-thrombi in small hepatic and portal venules, sinusoidal ischemic injury and hepatocyte apoptosis. In addition, thrombin may participate in fibrogenesis by the interaction with HSC via protease-activated receptors (PAR-1 and PAR-4) favouring a myo-fibroblast phenotype, may participate to fibronectin fibril assembly by HSC, may act as a chemoattractant for inflammatory cells triggering fibrogenesis. Altogether, these observations increase the interest on drugs interfering with the coagulation process in an antifibrotic perspective of potential clinical interest from the earliest stages of chronic hepatitis to cirrhosis. The in vitro and in vivo studies on these aspects will be the main focus of the manuscript.

Authors: M. Onisto , V. Masola et al
Affiliation: Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Tentative title: Heparanase: a multitasking protein involved in Extarcellular Matrix (ECM) remodeling and cellular signaling

Authors: Gianluca Di Cara 1,*, Maria Rita Marabeti 1,*, Rosa Musso 1, Ignazio Riili 2, Patrizia Cancemi 3^ and Ida Pucci Minafra 1^
Affiliation: 1 Centro di Oncobiologia Sperimentale, Università di Palermo, Italy
2 La Maddalena Hospital, Palermo, Italy
3 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università di Palermo, Italy
co-first Authors
^ co-corresponding Authors: Patrizia Cancemi 3^ and Ida Pucci Minafra 1^
Tentative title: New insights into the occurrence of Matrix Metalloproteases -2 and -9 in a cohort of breast cancer patients
Abstract: Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain where they fulfill the function of remodelling the extracellular matrix. About 26 family members, encoded by 24 genes, MMP-2 and MMP-9 have been regarded as the major responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur.
Present investigation represents the prosecution and upgrading of a study into the occurrence and intensity levels of MMP-2 and -9 in a large scale of breast cancer sera, testifying a differential involvement of the two enzymes in breast cancer progression.

Authors: Vinicius Guzzoni 1,*, Rita de Cássia Marqueti 2
Affiliation: 1 College of Physical Education, Brasil University, Taquaritinga, Brazil;
 2 University of Brasilia, Distrito Federal, Brazil
Tentative Title: Effects of Anabolic-Androgenic Steroids (AAS), Aging and Exercise Training on Tendon Homeostasis
Abstract: Tendons constitute important structures of musculoskeletal system that transmit muscle-generating tensile force to bones. They are comprised of tissue-specific cells, including tenoblasts and tenocytes, chondrocytes, synovial cells and vascular cells, which synthesize proteins of extracellular matrix (ECM). ECM is composed primarily of collagens, large proteoglycans and small leucine-rich proteoglycans. In this regard, there are various factors that substantially could affect tendon homeostasis, including anabolic androgenic steroids (AAS) and aging. The goal of this narrative review is aggregate findings regarding to the effects of AAS, aging on tendons homeostasis. Also whether exercise training modulates the responses triggered by AAS and aging is worthy of investigation. Data from the last years indicate detrimental effects of AAS and aging on skeletal muscle tissue, even though there are fewer evidences concerning their effects on tendon. In fact, high doses of AAS have been shown to affect the collagen metabolism, which might suppose that AAS would affect molecular or functional and ultrastructural properties of rat tendons. In fact, biomechanical changes and ECM remodeling, as evidenced by alterations on MMP-2 activity, were observed in response to high doses of AAS. Furthermore, concerns related to age-induced musculoskeletal adaptations have been a topic of interest in the scientific and medical communities. In this perspective, we have investigated the effects of aging on tendon homeostasis and the effects of exercise training, particularly resistance training (RT) on this matter. Consistently, we demonstrated that RT attenuated the age-related dysfunction of rat tendons. Noteworthy, while aging has been shown to downregulate the gene expression of key elements related to ECM remodeling, RT was effective to upregulate those ECM-related molecules. Therefore, RT might be considered as a potential intervention to prevent both aging-related loss in ECM proteins and attenuate the detrimental functional effects in tendons in response to aging, as ruptures and tendinopathies.

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