The Pathophysiological Significance of Fibulin-3

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-09, Vol.10 (9), p.1294
• Main Authors: Livingstone, Imogen, Uversky, Vladimir N, Furniss, Dominic, Wiberg, Akira
• Format: Article
• Language: English
• Subjects: Age; Animals; Binding sites; connective tissue; Connective tissues; Disease; Disease Models, Animal; EFEMP1; EFEMP1 gene; Epidermal growth factor; Extracellular matrix; Extracellular Matrix - enzymology; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - physiology; fibulin-3; Genetic diversity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humans; intrinsically disordered protein; Macular degeneration; Matrix protein; Metalloproteinase; Optic Disk Drusen - congenital; Optic Disk Drusen - genetics; Optic Disk Drusen - physiopathology; Phenotypes; Phosphorylation; Physiological aspects; Physiology; Point mutation; Proteins; Retinal degeneration; Review; Tissue inhibitor of metalloproteinase 3
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10091294

Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.