MFAP4

MFAP4 (microfibril-associated glycoprotein 4) is an extracellular matrix protein encoded by the MFAP4 gene. It is part of the MFAP family of proteoglycans, which are involved in cell adhesion, intercellular interactions and the assembly and/or maintenance of elastic fibres.[1]

MFAP4 is known to co-localise at sites rich in elastic fibres and is thought to interact with several proteins including FBN1, FBN2, tropoelastin and desmosine[2]. It has a relatively non-specific tissue expression pattern, with higher levels observed in organs such as the lungs and vasculature.[3]

Clinical relevance

Using MFAP4-deficient mouse models, studies have shown roles for MFAP4 in neointima formation[4] and asthma.[5]

Moreover, it has recently been shown that the glycosylation of MFAP4 is raised in the aortic extracellular matrix of Marfan syndrome patients using proteomics and gene expression levels of MFAP4 correlate with alterations in extracellular matrix genes within human aortic vascular smooth muscle cells.[6].

Potential biomarker

MFAP4 has received considerable attention as a possible biomarker for many conditions including Marfan syndrome,[6] surgical repair of abdominal aortic aneurysms,[7] cardiovascular disease,[8] COPD,[9] liver fibrosis,[10] and various cancers.[11]

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References
  1. "MFAP4 - Microfibril-associated glycoprotein 4 precursor - Homo sapiens (Human) - MFAP4 gene & protein".
  2. Pilecki B, et al. (Jan 2016). "Characterization of microfibrillar-associated protein 4 (MFAP4) as a tropoelastin- and fibrillin-binding protein involved in elastic fiber formation". Journal of Biological Chemistry. 291 (3): 1103–14. doi:10.1074/jbc.M115.681775. PMC 4714194. PMID 26601954.
  3. "Tissue expression of MFAP4 - Summary - The Human Protein Atlas". www.proteinatlas.org.
  4. Schlosser, et al. (Jan 2016). "MFAP4 Promotes Vascular Smooth Muscle Migration, Proliferation and Accelerates Neointima Formation". Arteriosclerosis, Thrombosis and Vascular Biology. 36 (1): 122–33. doi:10.1161/ATVBAHA.115.306672. PMID 26564819. S2CID 1740441.
  5. Pilecki, et al. (Sep 2015). "Microfibrillar-associated Protein 4 Modulates Airway Smooth Muscle Cell Phenotype in Experimental Asthma". Thorax. 70 (9): 862–72. doi:10.1136/thoraxjnl-2014-206609. PMID 26038533. S2CID 207032473.
  6. Yin, et al. (Sep 2019). "Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients". Arteriosclerosis, Thrombosis and Vascular Biology. 39 (9): 1859–1873. doi:10.1161/ATVBAHA.118.312175. PMC 6727943. PMID 31315432.
  7. Lindholt, et al. (Jun 2020). "High Plasma Microfibrillar-Associated Protein 4 Is Associated With Reduced Surgical Repair in Abdominal Aortic Aneurysms". Journal of Vascular Surgery. 71 (6): 1921–1929. doi:10.1016/j.jvs.2019.08.253. PMID 31784280.
  8. Wulf-Johansson, et al. (Dec 2013). "Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues: Clinical Evaluation of Serum MFAP4 and Its Association With Various Cardiovascular Conditions". PLOS ONE. 8 (12): e82243. doi:10.1371/journal.pone.0082243. PMC 3862580. PMID 24349233.
  9. Johansson, et al. (Sep 2014). "Microfibrillar-associated Protein 4: A Potential Biomarker of Chronic Obstructive Pulmonary Disease". Respiratory Medicine. 108 (9): 1336–44. doi:10.1016/j.rmed.2014.06.003. PMID 25022422.
  10. Saekmose, et al. (Oct 2015). "Microfibrillar-Associated Protein 4: A Potential Biomarker for Screening for Liver Fibrosis in a Mixed Patient Cohort". PLOS ONE. 10 (10): e0140418. doi:10.1371/journal.pone.0140418. PMC 4604125. PMID 26460565.
  11. Yang, et al. (Jan 2019). "Integrated Analysis of Microfibrillar-Associated Proteins Reveals MFAP4 as a Novel Biomarker in Human Cancers". Epigenomics. 11 (1): 1635–1651. doi:10.2217/epi-2018-0080. PMID 30089404.
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