Osteopontin: The Molecular Bridge between Fat and Cardiac–Renal Disorders

Abstract

Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the “cross roads” of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac–renal disorders ruled by OPN.

Physiological Changes and Pathological Pain Associated with Sedentary Lifestyle-Induced Body Systems Fat Accumulation and Their Modulation by Physical Exercise

“…Under chronic heart stresses (e.g., pressure overload, hypertrophy, cardiomyocyte injury), the quiescent cardiac fibro-adipocyte progenitors (FAPs; quiescent stem cells) become activated and are differentiated in two non-cardiac lineages, including intracardiac adipocytes and intracardiac fibroblast. This activation is mediated by osteopontin [274]. Osteopontin also acts on the cardiovascular system, causing arteriosclerosis, angiogenesis, myocardial remodeling [275], valvular stenosis, hypertrophy, myocardial infarction, heart failure [276], aortic disorders, and coronary artery disease [277].…”

Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality

“…However, results from later studies established a wider pattern of upregulation of OPN in fibrotic disease suggesting a dominant role in the pathogenesis of lung fibrosis ( 30 ). OPN may act as a cytokine and a transcription factor and is directly involved in extracellular matrix regulation and collagen expression in fibrotic disorders of the liver, kidneys and heart ( 31 , 32 ).…”

Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease

“…Osteopontin ( OPN ) is an extracellular matrix protein, with diverse functions, including growth factor, structural matrix protein, modulator of matrix-cell interactions, among others. Besides, due to the different post-translational modifications, OPN participate in several biological processes, mainly in the regulation of calcification, biomineralization and proinflammatory response [ 11 , 12 , 13 , 14 ]. The human OPN gene is located on chromosome 4 (4q21-23) and is formed by seven exons [ 13 ].…”

“…The human OPN gene is located on chromosome 4 (4q21-23) and is formed by seven exons [ 13 ]. This protein has pleiotropic effects, and it is expressed in several cell types such as osteocytes, osteoblasts, pre-osteoblasts, macrophages, T-cells, endothelial cells and fibroblasts, and in different tissues including bone, cartilage, vascular tissue, brain and kidney, with essential physiological and pathophysiological functions [ 11 , 13 , 14 , 15 ]. OPN also plays a preponderant role in different pathologies such as autoimmune disorders, chronic inflammatory diseases, distinct types of cancer, diabetes, cardiovascular diseases, among others [ 15 , 16 ].…”