|
Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the ''MMP7'' gene. Matrilysin was discovered by Sellers and Woessner in the uterus of the rat in 1988. The complementary DNA (cDNA) of human MMP7 was isolated in 1988 by Muller et al. MMP7 is a member of the matrix metalloproteinase (MMP) family consisting of structural-related zinc-dependent endopeptidases. The primary role of cleaved/activated MMP7 is to break down extracellular matrix by degrading macromolecules including casein, type I, II, IV, and V gelatins, fibronectin, and proteoglycan.〔 == Gene, regulation, and expression == The human MMP7 is located on chromosome 11 q22.3. ''MMP'' genes are clustered in q region of human Chromosome 11 including ''matrilysin, collagenase-1, stromelysin1, stromelysin-2, and metalloelastase'' genes. It consists of 267 amino acids. The cDNA of MMP7 is 49% homologous to stromelysin-1.〔 Comparing to other members of MMP family, MMP7 does not have a C-terminal protein domain. The promoter of the human MMP7 contains a TATA box, an activator protein 1 (AP-1) site, and two inverted polymavirus enhancer A-binding proteins 2 (PEA-3). The AP-1/PEA-3 binding motif is required and essential for MMP7 to be responsive to growth factors, oncogenes and phorbol ester. Also, the PEA and AP-1 are required for Matrilysin/CAT reporter constructs induced by tumor promoter 12-O-tetradecanoulphorbol-13-acetate (TPA) and epidermal growth factor (EGF). In addition, the high level expression of AP-1 and its binding proteins were found to be associated with mutant Ki-Ras suggesting the high expression of matrilysin in Ras activated cells is AP-1 dependent.〔 The expression of MMP7 is regulated by the Wnt/ β catenin signaling pathway, and mediated by transformation growth factor β (TGF-β).TGF-β stimulates ECM and suppresses the steady-state level of MMP7, stromelysin mRNAs, and secretion of zymogens. The isoforms of TGF-β inhibit MMP7 mRNA and protein in the human endometrium via progesterone mediated pathway. However, the opposite effects of TGF-β on MMP7 were observed among transformed cells. In human glioma cell lines and human squamous cell carcinoma cell line II-4, TGF-β stimulates the expression of MMP7 mRNA and proteins, and facilities the invasive behavior of cells. The promoter region of the human MMP7 gene contains two or more sites that are homologous to the NR-IL6 binding sequences indicating MMP7 can bind to IL-1 and IL-6. In addition, the level of MMP7 mRNA is elevated followed the treatment of tumor necrosis factor α (TNF- α) and IL-1 β in human mesangial cells.〔 MMP7 are commonly expressed in epithelial cells including ductal epithelium of exocrine glands in skin, salivary glands, pancreas, glandular epithelium of intestine and reproductive organ, liver, and breast. In addition, MMP7 is highly expressed in the luminal surface of dysplastic glands in human colorectal cancers.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「MMP7」の詳細全文を読む スポンサード リンク
|