Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

• Published in: International journal of molecular sciences Vol. 25; no. 12; p. 6591
• Main Authors: Fujita, Motomichi, Sasada, Manabu, Iyoda, Takuya, Fukai, Fumio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.06.2024; MDPI
• Subjects: Age; Aging; Aging - metabolism; Animals; Apoptosis; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cartilage; Cell Adhesion; Cell adhesion & migration; Cellular Senescence; communication network factor; Communications networks; Disease; Diseases; Extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - metabolism; Fibroblasts; Fibrosis; Growth factors; Health aspects; Humans; Integrins; Integrins - metabolism; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - pathology; Japan; Kinases; matricryptic site; matricryptins; Molecular Targeted Therapy; Morphology; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Osteoarthritis; Osteoarthritis - metabolism; Osteoarthritis - pathology; Oxidative stress; Pathology; Peptides; Physiological aspects; Physiology; Proteins; Review; Roles; Senescence; senescence-associated secretory phenotype; senomorphic drug; senotherapy; Signal Transduction; Japan; matricryptic site; matricryptins; senomorphic drug; periostin; osteopontin; PAI-1; senotherapy; tenascin-C; communication network factor; senescence-associated secretory phenotype
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126591

Senescence is a physiological and pathological cellular program triggered by various types of cellular stress. Senescent cells exhibit multiple characteristic changes. Among them, the characteristic flattened and enlarged morphology exhibited in senescent cells is observed regardless of the stimuli causing the senescence. Several studies have provided important insights into pro-adhesive properties of cellular senescence, suggesting that cell adhesion to the extracellular matrix (ECM), which is involved in characteristic morphological changes, may play pivotal roles in cellular senescence. Matricellular proteins, a group of structurally unrelated ECM molecules that are secreted into the extracellular environment, have the unique ability to control cell adhesion to the ECM by binding to cell adhesion receptors, including integrins. Recent reports have certified that matricellular proteins are closely involved in cellular senescence. Through this biological function, matricellular proteins are thought to play important roles in the pathogenesis of age-related diseases, including fibrosis, osteoarthritis, intervertebral disc degeneration, atherosclerosis, and cancer. This review outlines recent studies on the role of matricellular proteins in inducing cellular senescence. We highlight the role of integrin-mediated signaling in inducing cellular senescence and provide new therapeutic options for age-related diseases targeting matricellular proteins and integrins.