MMP 7 Human
Description
Introduction to MMP-7
MMP-7, also known as matrilysin, is a zinc- and calcium-dependent endopeptidase encoded by the MMP7 gene on human chromosome 11q22.3 . With a molecular weight of ~30 kDa, it is the smallest member of the matrix metalloproteinase (MMP) family and lacks the C-terminal hemopexin domain found in other MMPs . MMP-7 degrades extracellular matrix (ECM) components such as gelatin, fibronectin, proteoglycans, and elastin, while also cleaving non-ECM proteins like E-cadherin and Fas ligand . Its activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) and zinc-chelating agents .
Gene Structure and Regulation
The MMP7 promoter contains AP-1 and PEA-3 binding motifs, enabling responsiveness to growth factors (e.g., EGF), oncogenes (e.g., Ras), and inflammatory stimuli . Key regulatory features include:
Physiological Roles
MMP-7 is critical in:
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Tissue remodeling: Facilitates endometrial regeneration and biliary repair .
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Innate immunity: Activates intestinal α-defensins to combat pathogens .
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Wound healing: Processes growth factors (e.g., HB-EGF) to promote epithelial migration .
Cancer
MMP-7 is overexpressed in aggressive tumors (e.g., renal, gastric, and colorectal cancers) and promotes:
Cardiovascular Disease
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Atherosclerosis: MMP-7 destabilizes plaques by degrading elastin and inducing smooth muscle apoptosis .
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Stroke: Serum MMP-7 levels correlate with gut permeability and post-stroke infections .
Fibrotic Disorders
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Kidney fibrosis: Drives ECM accumulation via Wnt/β-catenin signaling .
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Liver fibrosis: Elevated in biliary atresia (median serum level: 64.25 ng/mL vs. 9.97 ng/mL in controls) .
Infectious and Immune Responses
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Bacterial/fungal infections: CpG DNA and β-glucans stimulate MMP-7 secretion in B-lymphocytes .
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Intestinal inflammation: Mediates TNF-α shedding and epithelial barrier dysfunction .
Biomarker Performance
| Condition | Sample Type | MMP-7 Cutoff | Sensitivity/Specificity | Source |
|---|---|---|---|---|
| Biliary atresia | Serum | 25.9 ng/mL | 86.9%/94.5% | |
| Carotid plaque instability | Plasma | 156–10,000 pg/mL (ELISA) | Correlates with symptom recency |
Detection Methods
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ELISA: Commercial kits (e.g., Biosensis BEK-2071) quantify MMP-7 in serum, plasma, and urine with sensitivity <6 pg/mL .
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Dried blood spots (DBS): MMP-7 remains stable at 30–37°C for 3 days, enabling field applications .
Therapeutic Targeting
Product Specs
Q&A
What validated methodologies exist for quantifying MMP-7 in human biospecimens?
Three principal approaches dominate MMP-7 measurement:
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ELISA platforms: Demonstrated 0.54–15.91 ng/mL dynamic range in serum/plasma with inter-assay CV <15%
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Proteomic workflows: Luminex xMAP technology achieves multiplexed MMP-7 quantification at 0.1 pg/mL sensitivity in cohort studies (n=9407)
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Transcriptomic validation: RNA-seq of kidney biopsies coupled with immunohistochemistry confirms tubular MMP-7 production (Nephroseq v5 database)
Table 1: MMP-7 detection performance across methodologies
How should researchers establish context-specific reference ranges for MMP-7?
Population stratification is critical given MMP-7's demographic variability:
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Sex differences: Healthy males exhibit 104% higher serum MMP-7 vs females (p=0.001)
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Developmental changes: Neonatal cholestasis cohorts show 29.4-fold MMP-7 elevation (10.54 vs 0.54 ng/mL)
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Disease-specific cutoffs:
Methodological recommendation: Perform ROC analysis stratified by age/sex using cohorts ≥500 participants to minimize type I errors .
How to resolve contradictions between circulating and tissue MMP-7 measurements?
Discordant findings require multi-compartment analysis:
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Renal disease paradox: FSGS shows 4.8× higher urinary MMP-7 despite normal serum levels (p<0.001)
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Lung-kidney axis: Serum MMP-7 predicts pulmonary fibrosis (β=-3.7% FVC/log-unit) but not diabetic nephropathy progression
Table 2: MMP-7 compartmental dynamics in major diseases
| Condition | Serum MMP-7 | Urine MMP-7 | Tissue MMP-7 | Key Driver |
|---|---|---|---|---|
| Biliary atresia | ↑↑↑ | – | ↑↑ | Hepatic stellate cells |
| FSGS | ↔ | ↑↑↑ | ↑↑ | Tubular epithelial |
| IPF | ↑↑↑ | – | ↑ | Alveolar macrophages |
What experimental designs optimize MMP-7's utility as a predictive biomarker?
Phase-adaptive approaches are essential:
Discovery phase
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Multi-omics integration: Combine proteomics (Olink), transcriptomics (Nephroseq), and histology
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Longitudinal sampling: 5-year intervals capture MMP-7's prognostic value for eGFR decline (β=-4.2 mL/min/year)
Validation phase
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Cohort selection:
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Endpoint standardization:
Should MMP-7 measurement replace traditional biomarkers in clinical trials?
Current evidence supports adjunctive rather than replacement roles:
Renal trials
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Adding uMMP-7 to MEST-C score improves IgAN risk prediction (ΔAUC +0.11)
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MMP-7/creatinine ratio outperforms proteinuria for fibrosis monitoring (r=0.73 vs 0.58)
Pulmonary trials
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Serum MMP-7 predicts mortality independent of HRCT findings (HR=2.2, p<0.001)
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Limitations: 24% inter-individual variability requires duplicate measurements
Synthesis and Future Directions
The Tromsø Study's 17-year follow-up (n=11,030) confirms MMP-7's role in subclinical fibrosis , while MESA cohort data (n=1,227) link 5.6 ng/mL MMP-7 thresholds to accelerated lung decline . Emerging solutions include:
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Point-of-care devices: CRISPR-based biosensors achieving 0.01 pg/mL detection in whole blood
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Therapeutic targeting: Galunisertib trials showing 38% MMP-7 reduction in hepatic fibrosis
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Multi-organ profiling: Machine learning models integrating hepatic/renal/pulmonary MMP-7 data
Product Science Overview
Matrix Metalloproteinase-7 (MMP-7), also known as matrilysin, is a member of the matrix metalloproteinase (MMP) family. This family consists of structurally related zinc-dependent endopeptidases that play a crucial role in the breakdown of extracellular matrix (ECM) components. MMP-7 is the smallest member of the MMP family and is encoded by the MMP7 gene located on human chromosome 11q21-q22 .
MMP-7 was first discovered by Sellers and Woessner in the uterus of the rat in 1988 . The complementary DNA (cDNA) of human MMP7 was isolated in the same year by Muller et al . Human MMP-7 has a molecular weight of approximately 30 kDa . Unlike other MMPs, MMP-7 lacks a conserved C-terminal hemopexin-like domain, which is typically involved in substrate specificity and interaction with tissue inhibitors of metalloproteinases (TIMPs) .
MMP-7 is primarily involved in the degradation of ECM components, including casein, type I, II, IV, and V gelatins, fibronectin, and proteoglycan . This enzyme is exclusively released by epithelial cells and is highly expressed in various cancer cells . MMP-7 plays a significant role in normal physiological processes such as embryonic development, reproduction, and tissue remodeling. Additionally, it is implicated in pathological processes like arthritis and metastasis .
Elevated expression of MMP-7 has been associated with the progression and metastasis of various cancers, including tongue squamous cell carcinoma (TSCC) . Studies have shown that high levels of MMP-7 promote cell proliferation, migration, and invasion in cancer cells . As a result, MMP-7 is considered a potential therapeutic target for cancer treatment.
