Matrix metalloproteinase 28, also known as epilysin, belongs to a family of proteins known as matrix metalloproteinases which are common to tissue regulation. Matrix metalloproteinases are commonly known to degrade the extracellular matrix, alongside regulating cell surface receptors MMP-28 releases growth factors and adhesion molecules to modulate inflammation.[8] MMP-28 is unique in that it can be found in many regular tissues, denoting a potential role in maintaining the healthy structure and function of most tissue. MMPs commonly modulate their expression via negative and positive feedback loops as a result of releasing and responding to growth hormones.
MMP-28 is less frequently found in tissues such as the brain, colon, heart, and lungs.[9] However, MMP-28 is expressed heavily in organs such as the testes. Epilysin is also found in high concentration in basal keratinocytes in injured skin, even at some distance away from the wound, showing a role in repairing damaged tissue. MMP-28 also can alter the cell membrane to become more adhesive, and not allowing the cell to migrate.[10]
MMP-28 is a 520 amino acid long protein. The estimated signal peptide sequence appears as a long tail of random coil coming off of the protein that helps to guide the protein to excretion with the sequence PRCGVTD.[11] The zinc binding catalytic site is tucked within an alpha helix within the center of the protein with a HEIGHTLGLTH sequence at positions 240–250 with a hemopexin-like domain. Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.
Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.
The full amino acid sequence is listed on uniprot.[12]
The overexpression of MMP-28 is linked to the metastasis of tumors in cancer.[13] Expression of MMP-28 can be linked to tumor diameter, depth of invasion, and stage of metastasis. In patients with positive overexpression of MMP-28, survival may be significantly less likely compared to negative expression of this protein, making it a potentially important marker for proactive prognosis of some forms of cancer.
MMP-28 may also play an important role in the breakdown ofmyelin,[14] an important component of nervous system functionality.Demyelination may interrupt nerve signaling or even halt it completely, which can create severe neurological effects such as multiple sclerosistransverse myelitis andneuromyelitis optica.[15]
^Marchenko GN, Strongin AY (March 2001). "MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors".Gene.265 (1–2):87–93.doi:10.1016/S0378-1119(01)00360-2.PMID11255011.
Illman SA, Keski-Oja J, Lohi J (September 2001). "Promoter characterization of the human and mouse epilysin (MMP-28) genes".Gene.275 (1):185–194.doi:10.1016/S0378-1119(01)00664-3.PMID11574168.
Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, et al. (January 2004). "Expression profiling of metalloproteinases and their inhibitors in cartilage".Arthritis and Rheumatism.50 (1):131–141.doi:10.1002/art.11433.PMID14730609.
Bister VO, Salmela MT, Karjalainen-Lindsberg ML, Uria J, Lohi J, Puolakkainen P, et al. (April 2004). "Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer".Digestive Diseases and Sciences.49 (4):653–661.doi:10.1023/B:DDAS.0000026314.12474.17.PMID15185874.S2CID34192223.
Momohara S, Okamoto H, Komiya K, Ikari K, Takeuchi M, Tomatsu T, Kamatani N (December 2004). "Matrix metalloproteinase 28/epilysin expression in cartilage from patients with rheumatoid arthritis and osteoarthritis: comment on the article by Kevorkian et al".Arthritis and Rheumatism.50 (12):4074–5, author reply 4075.doi:10.1002/art.20799.PMID15593191.
Renò F, Sabbatini M, Stella M, Magliacani G, Cannas M (2005). "Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars".Wound Repair and Regeneration.13 (3):255–261.doi:10.1111/j.1067-1927.2005.130307.x.PMID15953044.S2CID24640193.
