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MMP19

Official Full Name
matrix metallopeptidase 19
Background
This gene encodes a member of a family of proteins that are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded protein is secreted as an inactive proprotein, which is activated upon cleavage by extracellular proteases. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]
Synonyms
MMP19; matrix metallopeptidase 19; MMP18; RASI-1; matrix metalloproteinase-19; matrix metalloproteinase-18; matrix metalloproteinase RASI; matrix metalloproteinase-beta19; matrix metalloproteinase 19 , MMP18; RASI 1; MMP-18; MMP-19; matrix metalloproteinase 18; matrix metalloproteinase 19

MMP-19 is a member of matrix metalloproteinases (MMPs) and was first isolated from an autoimmune rheumatoid arthritis patient. MMP-19 is subsequently found in normal tissues such as the placenta, pancreas, lung, ovary, breast, and healthy epidermis. MMP-19 has the function of degrading extracellular matrix (ECM) such as collagen IV, gelatin, fibronectin, aggrecan, etc. in most MMPs families. It also plays a negative regulatory role in tumor angiogenesis and cancer cell growth and metastasis. MMP-19 can significantly inhibit the proliferation of human microvascular endothelial cells and reduce capillary-like structure formation, and can also isolate ECM-binding vascular endothelial growth factor (VEGF) subpopulation to attenuate the role of ECM in neovascularization. This is different from most MMPs mediated functions. 

Schematic representation of the NDRG2-mediated regulatory network responsible for the progression of GBC. Figure 1. Schematic representation of the NDRG2-mediated regulatory network responsible for the progression of GBC. (Dong GwangLee., et al. 2015)

Expression and Role of MMP-19

The MMP-19 gene was cloned in a rheumatoid arthritis patient and human liver cDNA library, which is widely expressed in normal human tissues, including tissues such as the breast, placenta, lung, pancreas, and healthy epidermis. In normal control patients with white matter, MMP-19 forms a microglia that expresses throughout the brain parenchyma and is also highly expressed in proliferating astrocytoma/glioma cells, which promotes cell invasion through the brain. Studies have shown that the protein product of the MMP-19 gene is highly expressed in ovarian borderline tumors and ovarian cancer. Studies have also shown that the expression of MMP-19 in nasopharyngeal carcinoma is significantly lower than that in normal nasopharyngeal epithelial tissue. The study found that MMP-19 is up-regulated in human gliomas and found that co-expression of MMP-19 and MMP-14 is significantly associated with the prognosis of glioma patients, suggesting that co-expression of these proteins can be used as sign of early diagnosis and independent prognosis.

The expression of MMP-19 is down-regulated during the formation of breast and skin malignant tumors, and tumor neovascularization and invasiveness are increased in MMP-19-expressing mice, suggesting that it plays a role in tumorigenesis and development. It is currently believed that MMP-19 plays a dual role in the overall occurrence and development of certain tumors. The study examined the role of MMP-19 in cell growth and tumorigenesis in human nasopharyngeal carcinoma, which significantly reduced cell clonality. In the initial formation of some malignant tumors, MMP-19 is not expressed or weakly expressed, thereby accelerating tumor growth and enhancing cell invasiveness. As malignant tumors grow, MMP-19 expression is enhanced. It regulates cell adhesion and proliferation through cytokines and insulin-like growth factors (IGFs) signaling pathways, but its expression may be lower than expression in normal tissues. This dual effect may be caused by the decreased sensitivity of tumor cells to MMP-19 as the tumor progresses.

MMP-19 and Tumor Development

As a negative effect of MMPs, MMP-19 can produce endogenous angiogenesis inhibitors by proteolytic cleavage, and strongly inhibit vascular endothelial cell migration and vascular proliferation. MMP-19 treatment of human plasminogen characteristic The lytic stalk generates three angiostatin-like fragments with molecular weights of 35, 38 and 42 kD. It can significantly inhibit the proliferation of human microvascular endothelial cells and reduce the formation of capillary-like structures. The expression of MMP-19 mRNA and MMP-19 protein in dermal fibroblasts strongly enhances tumor necrosis and localizes the tumor to a low concentration environment, thereby further activating TNF-α, inducing tumor proliferation and tumor angiogenesis.

References:

  1. Dong GwangLee ., Sang-Hyun Lee., Jang-Seong Kim., &   Jeong-Ki Min ..(2015). Loss of ndrg2 promotes epithelial-mesenchymal transition of gallbladder carcinoma cells through mmp-19-mediated slug expression. Journal of Hepatology, 63(6), S0168827815005486.
  2. Chirco, K. R. , Hazlewood, R. J. , Miller, K. , Workalemahu, G. , & Fingert, J. H. . (2016). Mmp19 expression in the human optic nerve. Molecular vision, 22, 1429-1436.
  3. Niu, H. , Li, F. , Wang, Q. , Ye, Z. , & Lin, Y. . (2018). High expression level of mmp9 is associated with poor prognosis in patients with clear cell renal carcinoma. PeerJ, 6(11), e5050.

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