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.
N1 - Funding Information:
The authors sincerely apologize if the work of any investigator has been omitted by mistake and is not referred to in this manuscript. This study was supported by NIH grant DK28492.
PY - 1998
Y1 - 1998
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 -