| First Author | Ota K | Year | 1998 |
| Journal | Kidney Int | Volume | 54 |
| Issue | 1 | Pages | 131-42 |
| PubMed ID | 9648071 | Mgi Jnum | J:48622 |
| Mgi Id | MGI:1271022 | Doi | 10.1046/j.1523-1755.1998.00XXX.x |
| Citation | Ota K, et al. (1998) Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor. Kidney Int 54(1):131-42 |
| abstractText | BACKGROUND: Extracellular matrix macromolecules regulate morphogenesis of embryonic organs, and are developmentally regulated. Their expression and turnover is regulated by matrix metalloproteinases (MMPs). Recently, an epithelial cell membrane associated metalloproteinase (MT-1-MMP) has been identified that acts as an activator of a secreted MMP-2, and is produced by mesenchymal fibroblasts. The activity of MMP-2 is inhibited by a soluble tissue inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown. METHODS: MT-1-MMP was cloned from embryonic mouse kidney cDNA library, and its spatio-temporal distribution during development in the context of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was studied. RESULTS: The cloned MT-1-MMP exhibited approximately 86% nucleotide sequence homology with human MT-1-MMP, and had a catalytic domain and a zinc binding site preceded by a RRKR furin recognition motif. A approximately 4.5 Kb MT-1-MMP mRNA transcript was detected, and its expression was developmentally regulated. A parallel developmental regulation of MMP-2 mRNA expression was also observed. TIMP-2 expression was also developmentally regulated, but lagged behind MT-1-MMP and MMP-2. By in situ hybridization, MT-1-MMP mRNA was seen to be confined to ureteric bud epithelia, and was absent in the mesenchyme, while MMP-2 was confined to the mesenchyme. MT-1-MMP protein expression was seen on ureteric bud epithelia, induced mesenchyme and nascent nephrons, and it was highest during mid gestation. Similar spatio-temporal expressions of MMP-2 and TIMP-2 proteins were observed. CONCLUSIONS: mRNAs of MT-MMP-1 and MMP-2 are expressed in the respective epithelial and mesenchymal compartments, while their proteins are co-expressed in the epithelia suggest that MT-1-MMP and MMP-2, in conjunction with TIMP-2, may be involved in paracrine/juxtacrine epithelial:mesenchymal interactions during metanephrogenesis. |
