Glycation-induced modification of tissue-specific ECM proteins: A pathophysiological mechanism in degenerative diseases

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 11; p. 129411
• Main Authors: Bansode, Sneha B., Gacche, Rajesh N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2019
• Subjects: advanced glycation end products; adverse effects; Cellular signalling; Degenerative diseases; disease course; drugs; Extracellular matrix; Extracellular Matrix Proteins - metabolism; functional properties; glycation; Glycation End Products, Advanced - metabolism; Glycosylation; Humans; integrins; Organ Specificity; pathogenesis; Protein glycation; RAGE; receptors; Signal Transduction; tissues; Extracellular matrix; RAGE; Degenerative diseases; Protein glycation; Cellular signalling
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.08.004

Glycation driven generation of advanced glycation end products (AGEs) and their patho-physiological role in human degenerative diseases has remained one of the thrust areas in the mainstream of disease biology. Glycation of extracellular matrix (ECM) proteins have deleterious effect on the mechanical and functional properties of tissues. Owing to the adverse pathophysiological concerns of glycation, there is a need to decipher the underlying mechanisms. AGE-modified ECM proteins affect the cell in the vicinity by altering protein structure-function, matrix-matrix or matrix-cell interaction and by activating signalling pathway through receptor for AGE. This review is intended for addressing the AGE-induced modification of tissue-specific ECM proteins and its implication in the pathogenesis of various organ-specific human ailments. The glycation affects the canonical cell behaviour due to alteration in the interaction of glycated ECM with receptors like integrins and discodin domain, and the signalling cues generated subsequently affect the downstream signalling pathways. Consequently, the variation of structural and functional properties of tissues due to matrix glycation helps in the initiation or progression of the disease condition. This review offers comprehensive knowledge about the remodelling of glycation induced ECM and tissue-specific pathological concerns. As glycation of ECM affects the normal tissues and cell behaviour, the scientific discourse may also provide cues for developing candidate drugs that may help in attenuating the adverse effects of AGEs and perhaps open a research window of tailoring novel strategies for the management of glycation induced human degenerative diseases. •ECM glycation alters the physiology of cellular growth, proliferation, migration and cell signalling pathways.•ECM Glycation adversely affects the neuronal system, lung homeostasis, cardiac system, bone metabolism, and renal function.•Glycated bone ECM influence bone remodelling and fragility.•There is need to develop glycation and AGE targeted therapeutic modalities.