Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy.

A. K. Sharma, Michael Mauer, Y. Kim, A. F. Michael

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We have previously characterized the evolution of renal cortical interstitial fibrosis in the rabbit model of unilateral ureteral obstruction (UUO). In our earlier report, we examined the extracellular matrix protein composition of the interstitial space. Of note, UUO was associated with the acquisition of prominent interstitial collagen IV immunoreactivity. Interstitial collagens I and III were also increased. In situ hybridization localized increased expression of collagens I and IV to cells of the interstitial space. In the current study, we examine metalloproteinase and metalloproteinase inhibitor expression in the obstructed renal cortex. Matrix metalloproteinase-2 is a metalloproteinase with activity against both collagen IV and denatured collagen I. At day 3 of UUO, both transcripts were significantly increased, although expression of these mRNAs was not different from controls after 7 and 16 days of UUO. Expression of mRNA of tissue inhibitor of the metalloproteinases (TIMP) was significantly increased in the UUO samples at all times, although it was maximal at day 3. Immunohistochemically, increased TIMP reactivity localized to the interstitial space, and TIMP mRNA expression was seen to parallel the interstitial macrophage infiltration that accompanies ureteteral obstruction. In contrast, TIMP-2 mRNA expression appeared to be biphasic, with peaks at both day 3 and day 16 of UUO. At day 7, expression was not different from controls. These data suggest a role for impaired matrix degradation in the development of interstitial fibrosis in the obstructed kidney, particularly at late times when collagen mRNA expression has returned to control values.

Original languageEnglish (US)
Pages (from-to)754-761
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume125
Issue number6
StatePublished - Jun 1 1995

Fingerprint

Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Ureteral Obstruction
Matrix Metalloproteinase 2
Collagen
Metalloproteases
Messenger RNA
Kidney
Fibrosis
Macrophages
Extracellular Matrix Proteins
Infiltration
In Situ Hybridization
Rabbits
Degradation
Chemical analysis

Cite this

Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy. / Sharma, A. K.; Mauer, Michael; Kim, Y.; Michael, A. F.

In: Journal of Laboratory and Clinical Medicine, Vol. 125, No. 6, 01.06.1995, p. 754-761.

Research output: Contribution to journalArticle

@article{c6f386f18c824eb99dc6148bfae8e89e,
title = "Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy.",
abstract = "We have previously characterized the evolution of renal cortical interstitial fibrosis in the rabbit model of unilateral ureteral obstruction (UUO). In our earlier report, we examined the extracellular matrix protein composition of the interstitial space. Of note, UUO was associated with the acquisition of prominent interstitial collagen IV immunoreactivity. Interstitial collagens I and III were also increased. In situ hybridization localized increased expression of collagens I and IV to cells of the interstitial space. In the current study, we examine metalloproteinase and metalloproteinase inhibitor expression in the obstructed renal cortex. Matrix metalloproteinase-2 is a metalloproteinase with activity against both collagen IV and denatured collagen I. At day 3 of UUO, both transcripts were significantly increased, although expression of these mRNAs was not different from controls after 7 and 16 days of UUO. Expression of mRNA of tissue inhibitor of the metalloproteinases (TIMP) was significantly increased in the UUO samples at all times, although it was maximal at day 3. Immunohistochemically, increased TIMP reactivity localized to the interstitial space, and TIMP mRNA expression was seen to parallel the interstitial macrophage infiltration that accompanies ureteteral obstruction. In contrast, TIMP-2 mRNA expression appeared to be biphasic, with peaks at both day 3 and day 16 of UUO. At day 7, expression was not different from controls. These data suggest a role for impaired matrix degradation in the development of interstitial fibrosis in the obstructed kidney, particularly at late times when collagen mRNA expression has returned to control values.",
author = "Sharma, {A. K.} and Michael Mauer and Y. Kim and Michael, {A. F.}",
year = "1995",
month = "6",
day = "1",
language = "English (US)",
volume = "125",
pages = "754--761",
journal = "Translational research : the journal of laboratory and clinical medicine",
issn = "1931-5244",
publisher = "Mosby Inc.",
number = "6",

}

TY - JOUR

T1 - Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy.

AU - Sharma, A. K.

AU - Mauer, Michael

AU - Kim, Y.

AU - Michael, A. F.

PY - 1995/6/1

Y1 - 1995/6/1

N2 - We have previously characterized the evolution of renal cortical interstitial fibrosis in the rabbit model of unilateral ureteral obstruction (UUO). In our earlier report, we examined the extracellular matrix protein composition of the interstitial space. Of note, UUO was associated with the acquisition of prominent interstitial collagen IV immunoreactivity. Interstitial collagens I and III were also increased. In situ hybridization localized increased expression of collagens I and IV to cells of the interstitial space. In the current study, we examine metalloproteinase and metalloproteinase inhibitor expression in the obstructed renal cortex. Matrix metalloproteinase-2 is a metalloproteinase with activity against both collagen IV and denatured collagen I. At day 3 of UUO, both transcripts were significantly increased, although expression of these mRNAs was not different from controls after 7 and 16 days of UUO. Expression of mRNA of tissue inhibitor of the metalloproteinases (TIMP) was significantly increased in the UUO samples at all times, although it was maximal at day 3. Immunohistochemically, increased TIMP reactivity localized to the interstitial space, and TIMP mRNA expression was seen to parallel the interstitial macrophage infiltration that accompanies ureteteral obstruction. In contrast, TIMP-2 mRNA expression appeared to be biphasic, with peaks at both day 3 and day 16 of UUO. At day 7, expression was not different from controls. These data suggest a role for impaired matrix degradation in the development of interstitial fibrosis in the obstructed kidney, particularly at late times when collagen mRNA expression has returned to control values.

AB - We have previously characterized the evolution of renal cortical interstitial fibrosis in the rabbit model of unilateral ureteral obstruction (UUO). In our earlier report, we examined the extracellular matrix protein composition of the interstitial space. Of note, UUO was associated with the acquisition of prominent interstitial collagen IV immunoreactivity. Interstitial collagens I and III were also increased. In situ hybridization localized increased expression of collagens I and IV to cells of the interstitial space. In the current study, we examine metalloproteinase and metalloproteinase inhibitor expression in the obstructed renal cortex. Matrix metalloproteinase-2 is a metalloproteinase with activity against both collagen IV and denatured collagen I. At day 3 of UUO, both transcripts were significantly increased, although expression of these mRNAs was not different from controls after 7 and 16 days of UUO. Expression of mRNA of tissue inhibitor of the metalloproteinases (TIMP) was significantly increased in the UUO samples at all times, although it was maximal at day 3. Immunohistochemically, increased TIMP reactivity localized to the interstitial space, and TIMP mRNA expression was seen to parallel the interstitial macrophage infiltration that accompanies ureteteral obstruction. In contrast, TIMP-2 mRNA expression appeared to be biphasic, with peaks at both day 3 and day 16 of UUO. At day 7, expression was not different from controls. These data suggest a role for impaired matrix degradation in the development of interstitial fibrosis in the obstructed kidney, particularly at late times when collagen mRNA expression has returned to control values.

UR - http://www.scopus.com/inward/record.url?scp=0029316690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029316690&partnerID=8YFLogxK

M3 - Article

VL - 125

SP - 754

EP - 761

JO - Translational research : the journal of laboratory and clinical medicine

JF - Translational research : the journal of laboratory and clinical medicine

SN - 1931-5244

IS - 6

ER -