TY - JOUR
T1 - Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor
AU - Ota, Kosuke
AU - Stetler-Stevenson, William G.
AU - Yang, Qiwei
AU - Kumar, Anil
AU - Wada, Jun
AU - Kashihara, Naoki
AU - Wallner, Elisabeth I.
AU - Kanwar, Yashpal S.
PY - 1998/1/1
Y1 - 1998/1/1
N2 - 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 ~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 ~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.
AB - 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 ~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 ~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.
KW - Embryonic kidney
KW - Gene and protein expression
KW - Membrane-type matrix
KW - Metalloproteinase-1
KW - Metanephrogenesis
KW - cDNA cloning
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U2 - 10.1046/j.1523-1755.1998.00975.x
DO - 10.1046/j.1523-1755.1998.00975.x
M3 - Article
C2 - 9648071
AN - SCOPUS:0031833237
VL - 54
SP - 131
EP - 142
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 1
ER -