Research

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17 pages, 3800 KiB

Open AccessArticle

Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ

by Alexander Eckersley, Matiss Ozols, Peikai Chen, Vivian Tam, Judith A. Hoyland, Andrew Trafford, Danny Chan and Michael J. Sherratt

Int. J. Mol. Sci. 2021, 22(19), 10408; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910408 - 27 Sep 2021

Cited by 7 | Viewed by 2325

Abstract

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting [...] Read more.

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus) identified 268 proteins with age-associated structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and -resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I α2, collagen II α1 and collagen V α1, were located within their triple-helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance. Several proteins (collagen V α1, collagen II α1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young samples, suggesting that some ageing mechanisms may act locally within tissues. This study not only reveals possible age-associated differences in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF as a proteomic tool to aid in biomarker discovery. Full article

(This article belongs to the Special Issue Extracellular Matrix Aging, Principles and Consequences)

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Review

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17 pages, 3334 KiB

Open AccessReview

Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix

by Joao Carlos Ribeiro-Silva, Patricia Nolasco, Jose Eduardo Krieger and Ayumi Aurea Miyakawa

Int. J. Mol. Sci. 2021, 22(18), 10175; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810175 - 21 Sep 2021

Cited by 13 | Viewed by 4560

Abstract

Vascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only [...] Read more.

Vascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only exacerbate aging, creating a self-sustaining inflammatory environment that also promotes vascular calcification. In this review, we highlight the role of crosstalk between smooth muscle cells and the vascular extracellular matrix (ECM) and how aging promotes smooth muscle cell phenotypes that ultimately lead to mechanical impairment of aging arteries. Understanding the underlying mechanisms and the role of associated changes in ECM during aging may contribute to new approaches to prevent or delay arterial aging and the onset of cardiovascular diseases. Full article

(This article belongs to the Special Issue Extracellular Matrix Aging, Principles and Consequences)

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20 pages, 2005 KiB

Open AccessReview

Employing Extracellular Matrix-Based Tissue Engineering Strategies for Age-Dependent Tissue Degenerations

by Yeonggwon Jo, Seung Hyeon Hwang and Jinah Jang

Int. J. Mol. Sci. 2021, 22(17), 9367; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179367 - 29 Aug 2021

Cited by 10 | Viewed by 3124

Abstract

Tissues and organs are not composed of solely cellular components; instead, they converge with an extracellular matrix (ECM). The composition and function of the ECM differ depending on tissue types. The ECM provides a microenvironment that is essential for cellular functionality and regulation. [...] Read more.

Tissues and organs are not composed of solely cellular components; instead, they converge with an extracellular matrix (ECM). The composition and function of the ECM differ depending on tissue types. The ECM provides a microenvironment that is essential for cellular functionality and regulation. However, during aging, the ECM undergoes significant changes along with the cellular components. The ECM constituents are over- or down-expressed, degraded, and deformed in senescence cells. ECM aging contributes to tissue dysfunction and failure of stem cell maintenance. Aging is the primary risk factor for prevalent diseases, and ECM aging is directly or indirectly correlated to it. Hence, rejuvenation strategies are necessitated to treat various age-associated symptoms. Recent rejuvenation strategies focus on the ECM as the basic biomaterial for regenerative therapies, such as tissue engineering. Modified and decellularized ECMs can be used to substitute aged ECMs and cell niches for culturing engineered tissues. Various tissue engineering approaches, including three-dimensional bioprinting, enable cell delivery and the fabrication of transplantable engineered tissues by employing ECM-based biomaterials. Full article

(This article belongs to the Special Issue Extracellular Matrix Aging, Principles and Consequences)

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