KOSEN 한인과학기술자네트워크

>각막에 있어서 MMP14의 역할에 대해서 알아보고자 합니다. >일반적으로 MMP14의 역할이 무엇인지 알고 싶습니다. >제가 알아본 바로는 MMP14가 각막에 손상을 입어서 그 손상을 회복시키는 동안에 혈관이 자라게끔 도와준다고 보았는데...MMP14가 증가하면 혈관이 생긴다고 보았는데요. 눈에 혈관이 생기면 우리가 물건을 쳐다보기가 어려워지잖아요. MMP14의 역할을 알려주세요 GENE FUNCTION Mignon et al. (1995) stated that membrane-type matrix metalloproteinase (MMP14) may be an activator of pro-gelatinase A (MMP2; 120360) and is expressed in fibroblast cells during both wound healing and human cancer progression. Ueda et al. (2002) investigated survivin gene and protein expression in a tumor-like benign disease, endometriosis, and correlated them with apoptosis and invasive phenotype of endometriotic tissues. Gene expression levels of survivin (603352), MMP2, MMP9 (120361), and MMP14 in 63 pigmented or nonpigmented endometriotic tissues surgically obtained from 35 women with endometriosis were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. Survivin, MMP2, MMP9, and MMP14 mRNA expression levels in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in nonpigmented lesions (P less than 0.05). There was a close correlation between survivin and MMP2, MMP9, and MMP14 gene expression levels in 63 endometriotic tissues examined (P less than 0.01). The authors concluded that upregulation of survivin and MMPs may cooperatively contribute to survival and invasion of endometriosis. Noda et al. (2003) studied MMPs and their activation in association with the pathogenesis of proliferative diabetic retinopathy (PDR). They demonstrated that pro-MMP2 was efficiently activated in the fibrovascular tissues of PDR, probably through interaction with MT1-MMP and TIMP2 (188825). The results suggested that MMP2 and MT1-MMP may be involved in the formation of the fibrovascular tissues. Hotary et al. (2003) found that MT1-MMP conferred human tumor cell lines with a 3-dimensional growth advantage in vitro and in vivo. The replicative advantage conferred by MT1-MMP required pericellular proteolysis of the extracellular matrix, as proliferation was suppressed by protease-resistant collagen gels. In the absence of proteolysis, tumor cells embedded in extracellular matrices were trapped in a compact, spherical configuration and were unable to undergo changes in cell shape or cytoskeletal reorganization required for 3-dimensional growth. REFERENCES 1. Holmbeck, K.; Bianco, P.; Caterina, J.; Yamada, S.; Kromer, M.; Kuznetsov, S. A.; Mankani, M.; Robey, P. G.; Poole, A. R.; Pidoux, I.; Ward, J. M.; Birkedal-Hansen, H. : MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99: 81-92, 1999. PubMed ID : 10520996 2. Hotary, K. B.; Allen, E. D.; Brooks, P. C.; Datta, N. S.; Long, M. W.; Weiss, S. J. : Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114: 33-45, 2003. PubMed ID : 12859896 3. Mignon, C.; Okada, A.; Mattei, M. G.; Basset, P. : Assignment of the human membrane-type matrix metalloproteinase (MMP14) gene to 14q11-q12 by in situ hybridization. Genomics 28: 360-361, 1995. PubMed ID : 8530054 4. Noda, K.; Ishida, S.; Inoue, M.; Obata, K.; Oguchi, Y.; Okada, Y.; Ikeda, E. : Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy. Invest. Ophthal. Vis. Sci. 44: 2163-2170, 2003. PubMed ID : 12714657 5. Oh, J.; Takahashi, R.; Adachi, E.; Kondo, S.; Kuratomi, S.; Noma, A.; Alexander, D. B.; Motoda, H.; Okada, A.; Seiki, M.; Itoh, T.; Itohara, S.; Takahashi, C.; Noda, M. : Mutations in two matrix metalloproteinase genes, MMP-2, and MT1-MMP, are synthetic lethal in mice. Oncogene 23: 5041-5048, 2004. PubMed ID : 15064723 6. Sato, H.; Takino, T.; Okada, Y.; Cao, J.; Shinagawa, A.; Yamamoto, E.; Seiki, M. : A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370: 61-65, 1994. PubMed ID : 8015608 7. Takino, T.; Sato, H.; Yamamoto, E.; Seiki, M. : Cloning of a human gene potentially encoding a novel matrix metalloproteinase having a C-terminal transmembrane domain. Gene 155: 293-298, 1995. PubMed ID : 7721107 8. Ueda, M.; Yamashita, Y.; Takehara, M.; Terai, Y.; Kumagai, K.; Ueki, K.; Kanda, K.; Yamaguchi, H.; Akise, D.; Hung, Y.-C.; Ueki, M. : Survivin gene expression in endometriosis. J. Clin. Endocr. Metab. 87: 3452-3459, 2002. PubMed ID : 12107265