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Matricellular Proteins in Human Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 6960

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Prof. Dr. Toshio Hattori

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Guest Editor

1. Visiting Professor, Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka 420-0881, Shizuoka, Japan
2. Emeritus Professor, Tohoku University, Sendai 980-8577, Miyagi, Japan
Interests: dengue; malaria; leptospirosis; HIV; tuberculosis; inflammation; galectins; osteopontin
Special Issues, Collections and Topics in MDPI journals

Dr. Yosuke Maeda

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Guest Editor

Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Interests: HIV; AIDS; retrovirus

Dr. Takashi Matsuba

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Guest Editor

Division of Infectious Disease Control and Prevention, Department of Animal Pharmaceutical Science, School of Pharmaceutical Science, Kyushu University of Health and Welfare, Nobeoka 882-8508, Japan
Interests: mechanisms of granuloma formation in tuberculosis; mechanisms of acquisition of higher virulence in mycobacteria

Special Issue Information

Dear Colleagues,

In 2000, Bornstein proposed that there was a family of secreted extracellular matrix (ECM) proteins that could be linked through their common functionality. He termed these proteins “matricellular” to highlight their influence on cell–matrix interactions. Matricellular proteins (MCPs) interact with cell surface receptors (such as integrins) and can bind to growth factors. On the basis of this definition, several proteins have now been identified as MCPs, including connective tissue growth factors, thrombospondin tenascins, osteopontins, galectins, SPARC, and SPARC-like proteins, CCN1-6 family of proteins, periostin, fibulins, Nov (CCN) proteins, and MMPs.

Matricellular proteins are expressed at high levels during development and in response to injury, and bind to many cell surface receptors, ECM proteins, growth factors, cytokines, and proteases. They generally induce the de-adhesion of normal cells, which contrasts the function of adhesivity of most ECM proteins.

MCPs play critical roles in cardiovascular and skeletal development, injury repair, fibrotic diseases, and cancer. In this Special Issue, therefore, the role of these proteins in tumor initiation, growth, invasion, metastasis, and angiogenesis will be included. Further, their potential as biomarkers and therapeutic targets should be presented. The plasma levels of matricellular proteins were found to reflect the disease severities in various infectious diseases in COVID-19 patients, probably because matricellular proteins are one of the most functional extracellular proteins that are associated with inflammatory edema. MCPs are also associated with cardiovascular events, independent of conventional cardiovascular risk factors. Thus, MCPs can also be a therapeutic target for cardiovascular diseases. Furthermore, these proteins are known to be involved in the central nervous system, skeletal muscle diseases, and interstitial diseases. In this Special Issue, the roles of MCPs in various human diseases will be presented to disclose their true faces.

Prof. Dr. Toshio Hattori
Dr. Yosuke Maeda
Dr. Takashi Matsuba
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

infectious diseases
COVID-19
lung
cardiovascular diseases
cancer
neurological disorders
ECM
MCPs

Published Papers (3 papers)

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Research

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16 pages, 11502 KiB

Open AccessArticle

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans

by Kenta Matsui, Sota Torii, Shigeru Hara, Kazuaki Maruyama, Tomio Arai and Kyoko Imanaka-Yoshida

Int. J. Mol. Sci. 2023, 24(12), 10184; https://doi.org/10.3390/ijms241210184 - 15 Jun 2023

Cited by 2 | Viewed by 1410

Abstract

Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling. Full article

(This article belongs to the Special Issue Matricellular Proteins in Human Diseases)

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17 pages, 5245 KiB

Open AccessArticle

Plasma N-Cleaved Galectin-9 Is a Surrogate Marker for Determining the Severity of COVID-19 and Monitoring the Therapeutic Effects of Tocilizumab

by Hiroko Iwasaki-Hozumi, Yosuke Maeda, Toshiro Niki, Haorile Chagan-Yasutan, Gaowa Bai, Takashi Matsuba, Daisuke Furushima, Yugo Ashino and Toshio Hattori

Int. J. Mol. Sci. 2023, 24(4), 3591; https://doi.org/10.3390/ijms24043591 - 10 Feb 2023

Cited by 3 | Viewed by 1472

Abstract

Galectin-9 (Gal-9) is known to contribute to antiviral responses in coronavirus disease 2019 (COVID-19). Increased circulating Gal-9 in COVID-19 is associated with COVID-19 severity. In a while, the linker-peptide of Gal-9 is susceptible to proteolysis that can cause the change or loss of Gal-9 activity. Here, we measured plasma levels of N-cleaved-Gal9, which is Gal9 carbohydrate-recognition domain at the N-terminus (NCRD) with attached truncated linker peptide that differs in length depending on the type of proteases, in COVID-19. We also investigated the time course of plasma N-cleaved-Gal9 levels in severe COVID-19 treated with tocilizumab (TCZ). As a result, we observed an increase in plasma N-cleaved-Gal9 levels in COVID-19 and its higher levels in COVID-19 with pneumonia compared to the mild cases (healthy: 326.1 pg/mL, mild: 698.0 pg/mL, and with pneumonia: 1570 pg/mL). N-cleaved-Gal9 levels were associated with lymphocyte counts, C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R), D-dimer, and ferritin levels, and ratio of percutaneous oxygen saturation to fraction of inspiratory oxygen (S/F ratio) in COVID-19 with pneumonia and discriminated different severity groups with high accuracy (area under the curve (AUC): 0.9076). Both N-cleaved-Gal9 and sIL-2R levels were associated with plasma matrix metalloprotease (MMP)-9 levels in COVID-19 with pneumonia. Furthermore, a decrease in N-cleaved-Gal9 levels was associated with a decrease of sIL-2R levels during TCZ treatment. N-cleaved-Gal9 levels showed a moderate accuracy (AUC: 0.8438) for discriminating the period before TCZ from the recovery phase. These data illustrate that plasma N-cleaved-Gal9 is a potential surrogate marker for assessing COVID-19 severity and the therapeutic effects of TCZ. Full article

(This article belongs to the Special Issue Matricellular Proteins in Human Diseases)

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Review

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25 pages, 3117 KiB

Open AccessReview

Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin

by Erna Raja, Maria Thea Rane Dela Cruz Clarin and Hiromi Yanagisawa

Int. J. Mol. Sci. 2023, 24(18), 14274; https://doi.org/10.3390/ijms241814274 - 19 Sep 2023

Cited by 1 | Viewed by 3514

Abstract

Matricellular proteins are secreted extracellular proteins that bear no primary structural functions but play crucial roles in tissue remodeling during development, homeostasis, and aging. Despite their low expression after birth, matricellular proteins within skin compartments support the structural function of many extracellular matrix proteins, such as collagens. In this review, we summarize the function of matricellular proteins in skin stem cell niches that influence stem cells’ fate and self-renewal ability. In the epidermal stem cell niche, fibulin 7 promotes epidermal stem cells’ heterogeneity and fitness into old age, and the transforming growth factor-β—induced protein ig-h3 (TGFBI)—enhances epidermal stem cell growth and wound healing. In the hair follicle stem cell niche, matricellular proteins such as periostin, tenascin C, SPARC, fibulin 1, CCN2, and R-Spondin 2 and 3 modulate stem cell activity during the hair cycle and may stabilize arrector pili muscle attachment to the hair follicle during piloerections (goosebumps). In skin wound healing, matricellular proteins are upregulated, and their functions have been examined in various gain-and-loss-of-function studies. However, much remains unknown concerning whether these proteins modulate skin stem cell behavior, plasticity, or cell–cell communications during wound healing and aging, leaving a new avenue for future studies. Full article

(This article belongs to the Special Issue Matricellular Proteins in Human Diseases)

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