The Pathophysiological Significance of Fibulin-3
Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the <i>EFEMP1</i> gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this fa...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1294 |
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| author | Imogen Livingstone Vladimir N. Uversky Dominic Furniss Akira Wiberg |
| author_facet | Imogen Livingstone Vladimir N. Uversky Dominic Furniss Akira Wiberg |
| author_sort | Imogen Livingstone |
| collection | DOAJ |
| description | Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the <i>EFEMP1</i> 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 <i>EFEMP1</i> causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). <i>EFEMP1</i> 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, <i>EFEMP1</i> 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. |
| first_indexed | 2024-03-10T16:29:18Z |
| format | Article |
| id | doaj.art-0e52acec6510438b99ceafa16347448e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:29:18Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-0e52acec6510438b99ceafa16347448e2023-11-20T12:55:55ZengMDPI AGBiomolecules2218-273X2020-09-01109129410.3390/biom10091294The Pathophysiological Significance of Fibulin-3Imogen Livingstone0Vladimir N. Uversky1Dominic Furniss2Akira Wiberg3Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UKLaboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Pushchino 142290, Moscow Region, RussiaNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UKNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UKFibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the <i>EFEMP1</i> 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 <i>EFEMP1</i> causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). <i>EFEMP1</i> 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, <i>EFEMP1</i> 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.https://www.mdpi.com/2218-273X/10/9/1294fibulin-3EFEMP1extracellular matrixconnective tissuegenome-wide association studyintrinsically disordered protein |
| spellingShingle | Imogen Livingstone Vladimir N. Uversky Dominic Furniss Akira Wiberg The Pathophysiological Significance of Fibulin-3 Biomolecules fibulin-3 EFEMP1 extracellular matrix connective tissue genome-wide association study intrinsically disordered protein |
| title | The Pathophysiological Significance of Fibulin-3 |
| title_full | The Pathophysiological Significance of Fibulin-3 |
| title_fullStr | The Pathophysiological Significance of Fibulin-3 |
| title_full_unstemmed | The Pathophysiological Significance of Fibulin-3 |
| title_short | The Pathophysiological Significance of Fibulin-3 |
| title_sort | pathophysiological significance of fibulin 3 |
| topic | fibulin-3 EFEMP1 extracellular matrix connective tissue genome-wide association study intrinsically disordered protein |
| url | https://www.mdpi.com/2218-273X/10/9/1294 |
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