Disease relevance of MMP28

• An injury of epidermis was needed for epilysin induction as it was upregulated in ulcerated pyogenic granulomas and in suction blisters but was not detected in intact acanthotic or normal skin [1].
• Unlike many other matrix metalloproteinases, epilysin was not detected in the invading cancer cell nests of sclerosing basal or squamous cell cancers of various grades [1].
• The aim of this study was to characterize in different types of wounds, skin cancers, and keratinocyte cultures factors that contribute to epilysin expression in vivo, as well as how and where it is induced in relation to other matrix metalloproteinases [1].
• Matrix metalloproteinase 28/epilysin expression in cartilage from patients with rheumatoid arthritis and osteoarthritis: comment on the article by Kevorkian et al [2].
• The broad range of expression in carcinomas as well as normal adult and fetal tissues suggests an important functional role for MMP-28 [3].

High impact information on MMP28

• Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils [4].
• We have cloned a new human matrix metalloproteinase (MMP-28, epilysin) from human keratinocyte and testis cDNA libraries [5].
• Like most MMPs, epilysin contains a signal sequence, a prodomain with a PRCGVTD sequence, a zinc-binding catalytic domain with an HEIGHTLGLTH sequence, and a hemopexin-like domain [5].
• Recombinant epilysin degraded casein in a zymography assay, and its proteolytic activity was inhibited by EDTA and by batimastat, a selective MMP inhibitor [5].
• In addition, epilysin has a furin activation sequence (RRKKR) but has no transmembrane sequence [5].

Biological context of MMP28

• Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair [1].
• When primary keratinocytes were stimulated with tumor necrosis factor alpha, upregulation of epilysin mRNA was evident within 24-48 h as measured by quantitative reverse transcription polymerase chain reaction [1].
• Another novel feature of epilysin is that exon 4 is alternatively spliced to a transcript that does not encode the N-terminal half of the catalytic domain [5].
• For reporter gene assays a series of constructs with fragments of increasing length of the epilysin promoter were coupled to the firefly luciferase gene [6].
• The genomic MMP-28 gene uniquely mapped to chromosome 17q11.2 includes eight exons and seven introns [3].

Anatomical context of MMP28

• In primary keratinocyte, HaCaT, and A431 carcinoma cell cultures none of the 10 other growth factors or extracellular matrices studied were able to upregulate epilysin expression [1].
• Additionally, we have shown that in cartilage the median level of steady-state mRNA for MMP13 is approximately 20-fold higher than MMP28 and approximately 1,500-fold higher than ADAMTS16, with expression of this latter gene approximately 150-fold higher in synovium than cartilage [7].
• Northern hybridization of tissue RNA indicated that epilysin is expressed at high levels in testis and at lower levels in lungs, heart, colon, intestine, and brain [5].
• Further, we found that epilysin and the recombinant hemopexin domain were targeted to the surface of epithelial cells [8].
• MMP-26 was detected in migrating enterocytes, unlike MMP-28 [9].

Associations of MMP28 with chemical compounds

• MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors [3].

Regulatory relationships of MMP28

• Current results indicate that epilysin can induce EMT and cell invasion through a TGF-beta-dependent mechanism suggesting novel biological roles for this enzyme in the regulation of epithelial cell function and in the induction of carcinogenesis [8].

Other interactions of MMP28

• Our results indicate that epilysin is produced by the mitotic Ki-67-positive keratinocytes distal from the wound edge in both acute and chronic wounds and that it does not generally colocalize with collagenase-1, stromelysin-2, or 92 kDa gelatinase in migrating keratinocytes [1].
• Epilysin (MMP-28) is the newest member of the matrix metalloproteinase enzyme family [1].
• In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed [10].
• We examined the profile of three recently cloned MMPs, MMP-21, MMP-26, and MMP-28, in melanomas in vivo and in culture [11].
• RNase protection assay with various cell lines indicated that epilysin was selectively expressed in keratinocytes [5].

Analytical, diagnostic and therapeutic context of MMP28

• MMP-28 immunohistochemistry revealed a light protein presence in normotrophic scar keratinocytes and a strong MMP-28 positivity in hypertrophic scar keratinocytes in control conditions, while compression increased MMP-28 staining in normotrophic scar and induced a significant reduction of the protein presence in hypertrophic scar keratinocytes [12].
• Analysis of MMP-28 protein secretion, assessed by Western blot and beta-casein zymography in scar conditioned media, revealed that normotrophic scar did not release MMP-28 in any condition while hypertrophic scar released active MMP-28 both in control conditions and after compression [12].
• By using RT-PCR, we found that expression of MMP-28 was significantly higher in 92 oral squamous cell carcinomas (OSCCs) (52/92, 56.5%) than in seven oral premalignant lesions (OPMLs) (0/7, 0%) (P=0.004) [13].

References