Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor

Kosuke Ota, William G. Stetler-Stevenson, Qiwei Yang, Anil Kumar, Jun Wada, Naoki Kashihara, Elisabeth I. Wallner, Yashpal S. Kanwar

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalKidney International
Volume54
Issue number1
DOIs
StatePublished - Jan 1 1998

Fingerprint

Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Organism Cloning
Tissue Inhibitor of Metalloproteinase-2
Mesoderm
Messenger RNA
Matrix Metalloproteinase 1
Matrix Metalloproteinase Inhibitors
Epithelium
Secreted Matrix Metalloproteinases
Furin
Kidney
Proteins
Nephrons
Metalloproteases
Sequence Homology
Matrix Metalloproteinases
Gene Library
Morphogenesis
In Situ Hybridization

Keywords

  • Embryonic kidney
  • Gene and protein expression
  • Membrane-type matrix
  • Metalloproteinase-1
  • Metanephrogenesis
  • cDNA cloning

ASJC Scopus subject areas

  • Nephrology

Cite this

Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor. / Ota, Kosuke; Stetler-Stevenson, William G.; Yang, Qiwei; Kumar, Anil; Wada, Jun; Kashihara, Naoki; Wallner, Elisabeth I.; Kanwar, Yashpal S.

In: Kidney International, Vol. 54, No. 1, 01.01.1998, p. 131-142.

Research output: Contribution to journalArticle

Ota, Kosuke ; Stetler-Stevenson, William G. ; Yang, Qiwei ; Kumar, Anil ; Wada, Jun ; Kashihara, Naoki ; Wallner, Elisabeth I. ; Kanwar, Yashpal S. / Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor. In: Kidney International. 1998 ; Vol. 54, No. 1. pp. 131-142.
@article{5511bd891baa41a391be95e6180f296d,
title = "Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor",
abstract = "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.",
keywords = "Embryonic kidney, Gene and protein expression, Membrane-type matrix, Metalloproteinase-1, Metanephrogenesis, cDNA cloning",
author = "Kosuke Ota and Stetler-Stevenson, {William G.} and Qiwei Yang and Anil Kumar and Jun Wada and Naoki Kashihara and Wallner, {Elisabeth I.} and Kanwar, {Yashpal S.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1046/j.1523-1755.1998.00975.x",
language = "English (US)",
volume = "54",
pages = "131--142",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=0031833237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031833237&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.1998.00975.x

DO - 10.1046/j.1523-1755.1998.00975.x

M3 - Article

VL - 54

SP - 131

EP - 142

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -