elastin and Metabolic-Diseases

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.

Topics: Animals; Collagen; Diabetes Mellitus; Elastin; Extracellular Matrix; Homeostasis; Humans; Insulin Resistance; Integrins; Laminin; Metabolic Diseases; Mice; Muscle, Skeletal; Rats

The organization of the tropoelastin gene is similar to that of other genes coding for matrix proteins in that the exons code for distinct domains of the protein. An unusual feature of tropoelastin expression is that the primary transcript of the gene coding for tropoelastin undergoes extensive, developmentally regulated alternative splicing, resulting in numerous protein isoforms. Although the significance of this heterogeneity is unknown, the multiple sequence variations may affect the function of tropoelastin. Without an understanding of the importance of the domains of tropoelastin and the process of fibrillogenesis, characterization of defects resulting in aberrant elastin production will be hindered. In this update, we review recent findings on tropoelastin and speculate as to the structural and regulatory role of various regions of this matrix protein.

Topics: Amino Acid Sequence; Animals; Base Sequence; Elastin; Genetic Variation; Humans; Metabolic Diseases; Molecular Sequence Data; RNA Splicing; RNA, Messenger; Structure-Activity Relationship; Tropoelastin

Topics: Aging; Amino Acids; Aneurysm; Animals; Arteriosclerosis; Brain Diseases; Copper; Deficiency Diseases; Elastic Tissue; Elastin; Endocardial Fibroelastosis; Growth Disorders; Hair; Humans; Inflammation; Lathyrism; Marfan Syndrome; Metabolic Diseases; Respiratory Tract Diseases; Skin Diseases

Topics: Arteries; Arteriosclerosis; Cholesterol; Collagen; Elastin; Glycosaminoglycans; Humans; Hypertension; L-Lactate Dehydrogenase; Macromolecular Substances; Metabolic Diseases; Necrosis; Oxidoreductases; Sclerosis; Thrombosis; Time Factors; Vasa Vasorum

Pseudoxanthoma elasticum (PXE) is a heritable disorder mainly characterized by calcified elastic fibers in cutaneous, ocular, and vascular tissues. PXE is caused by mutations in ABCC6, a gene encoding an ABC transporter predominantly expressed in liver and kidneys. The functional relationship between ABCC6 and elastic fiber calcification is unknown. We speculated that ABCC6 deficiency in PXE patients induces a persistent imbalance in circulating metabolite(s), which may impair the synthetic abilities of normal elastoblasts or specifically alter elastic fiber assembly. Therefore, we compared the deposition of elastic fiber proteins in cultures of fibroblasts derived from PXE and unaffected individuals. PXE fibroblasts cultured with normal human serum expressed and deposited increased amounts of proteins, but structurally normal elastic fibers. Interestingly, normal and PXE fibroblasts as well as normal smooth muscle cells deposited abnormal aggregates of elastic fibers when maintained in the presence of serum from PXE patients. The expression of tropoelastin and other elastic fiber-associated genes was not significantly modulated by the presence of PXE serum. These results indicated that certain metabolites present in PXE sera interfered with the normal assembly of elastic fibers in vitro and suggested that PXE is a primary metabolic disorder with secondary connective tissue manifestations.

Topics: Blood Proteins; Cardiovascular System; Cells, Cultured; Child; Connective Tissue; Elastic Tissue; Elastin; Eye; Female; Fibroblasts; Gene Expression Regulation; Humans; Male; Metabolic Diseases; Multidrug Resistance-Associated Proteins; Muscle, Smooth; Mutation; Pseudoxanthoma Elasticum; Skin; Tropoelastin