Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R

AbstractThe brain extracellular matrix (ECM) consists of extremely long-lived proteins that assemble around neurons and synapses, to stabilize them. The ECM is thought to change only rarely, in relation to neuronal plasticity, through ECM proteolysis and renewed protein synthesis. We report here an alternative ECM remodeling mechanism, based on the recycling of ECM molecules. Using multiple ECM labeling and imaging assays, from super-resolution optical imaging to nanoscale secondary ion mass spectrometry, both in culture and in brain slices, we find that a key ECM protein, Tenascin-R, is frequently endocytosed, and later resurfaces, preferentially near synapses. The TNR molecules complete this cycle within ~3 days, in an activity-dependent fashion. Interfering with the recycling process perturbs severely neuronal function, strongly reducing synaptic vesicle exo- and endocytosis. We conclude that the neuronal ECM can be remodeled frequently through mechanisms that involve endocytosis and recycling of ECM proteins.

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The monocyte chemotactic protein synthesis inhibitor bindarit prevents mesangial cell proliferation and extracellular matrix remodeling

Pharmacological Research ◽

10.1016/j.phrs.2012.09.006 ◽

2012 ◽

Vol 66 (6) ◽

pp. 526-535 ◽

Cited By ~ 8

Author(s):

Sara Paccosi ◽

Claudia Musilli ◽

Giorgina Mangano ◽

Angelo Guglielmotti ◽

Astrid Parenti

Keyword(s):

Extracellular Matrix ◽

Cell Proliferation ◽

Protein Synthesis ◽

Mesangial Cell ◽

Protein Synthesis Inhibitor ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Synthesis Inhibitor ◽

Chemotactic Protein ◽

Mesangial Cell Proliferation

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Tumor Extracellular Matrix Remodeling: New Perspectives as a Circulating Tool in the Diagnosis and Prognosis of Solid Tumors

Cells ◽

10.3390/cells8020081 ◽

2019 ◽

Vol 8 (2) ◽

pp. 81 ◽

Cited By ~ 15

Author(s):

Marta Giussani ◽

Tiziana Triulzi ◽

Gabriella Sozzi ◽

Elda Tagliabue

Keyword(s):

Extracellular Matrix ◽

Tumor Microenvironment ◽

Tumor Tissue ◽

Prognostic Markers ◽

Complex Mixture ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Diagnosis And Prognosis ◽

Novel Concept

: In recent years, it has become increasingly evident that cancer cells and the local microenvironment are crucial in the development and progression of tumors. One of the major components of the tumor microenvironment is the extracellular matrix (ECM), which comprises a complex mixture of components, including proteins, glycoproteins, proteoglycans, and polysaccharides. In addition to providing structural and biochemical support to tumor tissue, the ECM undergoes remodeling that alters the biochemical and mechanical properties of the tumor microenvironment and contributes to tumor progression and resistance to therapy. A novel concept has emerged, in which tumor-driven ECM remodeling affects the release of ECM components into peripheral blood, the levels of which are potential diagnostic or prognostic markers for tumors. This review discusses the most recent evidence on ECM remodeling-derived signals that are detectable in the bloodstream, as new early diagnostic and risk prediction tools for the most frequent solid cancers.

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Exercise-induced increases in insulin sensitivity after bariatric surgery are mediated by muscle extracellular matrix remodeling

10.2337/figshare.12272783.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Wagner S. Dantas ◽

Hamilton Roschel ◽

Igor H. Murai ◽

Saulo Gil ◽

...

Keyword(s):

Insulin Resistance ◽

Bariatric Surgery ◽

Extracellular Matrix ◽

Insulin Sensitivity ◽

Exercise Training ◽

Transforming Growth Factor ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Exercise Induced

Exercise seems to enhance the beneficial effect of bariatric surgery (RYGB) on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underly these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB or standard of care (RYGB). Insulin sensitivity was assessed by OGTT. Muscle biopsies were obtained at baseline, and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index - RYGB: +123% vs. RYGB + ET: +325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I - RYGB: -41% vs. RYGB + ET: -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-beta 1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle extracellular matrix remodeling.

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Understanding the mechanisms that determine extracellular matrix remodeling in the infarcted myocardium

Biochemical Society Transactions ◽

10.1042/bst20190113 ◽

2019 ◽

Vol 47 (6) ◽

pp. 1679-1687

Author(s):

Mavis A.A. Tenkorang ◽

Upendra Chalise ◽

Michael J. Daseke, II ◽

Shelby R. Konfrst ◽

Merry L. Lindsey

Keyword(s):

Myocardial Infarction ◽

Extracellular Matrix ◽

Wound Healing ◽

Inflammatory Response ◽

Current Knowledge ◽

Scar Formation ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Infarcted Myocardium

Myocardial Infarction (MI) initiates a series of wound healing events that begins with up-regulation of an inflammatory response and culminates in scar formation. The extracellular matrix (ECM) is intricately involved in all stages from initial break down of existing ECM to synthesis of new ECM to form the scar. This review will summarize our current knowledge on the processes involved in ECM remodeling after MI and identify the gaps that still need to be filled.

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Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms20194888 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4888 ◽

Cited By ~ 17

Author(s):

Ruiz-Ojeda ◽

Méndez-Gutiérrez ◽

Aguilera ◽

Plaza-Díaz

Keyword(s):

Extracellular Matrix ◽

Adipose Tissue ◽

Metabolic Diseases ◽

Tissue Expansion ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Survival And Development ◽

Tissue Receptors

The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

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Exercise-induced increases in insulin sensitivity after bariatric surgery are mediated by muscle extracellular matrix remodeling

10.2337/figshare.12272783.v2 ◽

2021 ◽

Author(s):

Wagner S. Dantas ◽

Hamilton Roschel ◽

Igor H. Murai ◽

Saulo Gil ◽

Gangarao Davuluri ◽

...

Keyword(s):

Insulin Resistance ◽

Bariatric Surgery ◽

Extracellular Matrix ◽

Insulin Sensitivity ◽

Exercise Training ◽

Transforming Growth Factor ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Exercise Induced

Exercise seems to enhance the beneficial effect of bariatric surgery (RYGB) on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underly these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB or standard of care (RYGB). Insulin sensitivity was assessed by OGTT. Muscle biopsies were obtained at baseline, and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index - RYGB: +123% vs. RYGB + ET: +325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I - RYGB: -41% vs. RYGB + ET: -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-beta 1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle extracellular matrix remodeling.

Download Full-text

Exercise-induced increases in insulin sensitivity after bariatric surgery are mediated by muscle extracellular matrix remodeling

10.2337/figshare.12272783 ◽

2020 ◽

Author(s):

Ada Admin ◽

Wagner S. Dantas ◽

Hamilton Roschel ◽

Igor H. Murai ◽

Saulo Gil ◽

...

Keyword(s):

Insulin Resistance ◽

Bariatric Surgery ◽

Extracellular Matrix ◽

Insulin Sensitivity ◽

Exercise Training ◽

Transforming Growth Factor ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Ecm Remodeling ◽

Exercise Induced

Exercise seems to enhance the beneficial effect of bariatric surgery (RYGB) on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underly these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB or standard of care (RYGB). Insulin sensitivity was assessed by OGTT. Muscle biopsies were obtained at baseline, and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index - RYGB: +123% vs. RYGB + ET: +325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I - RYGB: -41% vs. RYGB + ET: -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-beta 1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle extracellular matrix remodeling.

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Faculty Opinions recommendation of Sweet, yet underappreciated: Proteoglycans and extracellular matrix remodeling in heart disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732498270.793541733 ◽

2018 ◽

Author(s):

Nikos Karamanos

Keyword(s):

Extracellular Matrix ◽

Heart Disease ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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The Dynamic Interaction between Extracellular Matrix Remodeling and Breast Tumor Progression

Cells ◽

10.3390/cells10051046 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1046

Author(s):

Jorge Martinez ◽

Patricio C. Smith

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Cell Metabolism ◽

Breast Tumors ◽

Extracellular Matrix Remodeling ◽

Type I ◽

Matrix Remodeling ◽

Desmoplastic Reaction ◽

The Impact

Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as “desmoplastic reaction”. This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.

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