Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome

Velidi H. Rao, George E. Lees, Clifford E. Kashtan, Duane C. Delimont, Rakesh K Singh, Daniel T. Meehan, Gautam Bhattacharya, Brian R. Berridge, Dominic E Cosgrove

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) play an important regulatory role in many biological and pathological processes and their specific role in Alport syndrome (AS) is not yet clearly defined. In this study, the naturally occurring canine X-linked AS was used to demonstrate a potential role for MMP-3 and MMP-7 in Alport renal pathogenesis. Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS. In the present study, we examined necropsy samples of renal cortex from normal and XLAS dogs for MMP-3 and MMP-7 as they have the potential to activate MMP-2 and MMP-9. Immunohistochemical analysis showed strong immunostaining for both MMP-3 and MMP-7 in the interstitial space of XLAS kidneys, while virtually no immunostaining was observed in similar fields from normal dogs. RT-PCR and casein zymography confirmed that both mRNA transcripts and activities of MMP-3 and MMP-7 are elevated in XLAS kidneys. The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS. Thus, these data further implicate a role for the MMPs in progressive renal pathogenesis associated with AS.

Original languageEnglish (US)
Pages (from-to)732-739
Number of pages8
JournalPediatric Nephrology
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2005

Fingerprint

Matrix Metalloproteinase 7
Hereditary Nephritis
Matrix Metalloproteinase 3
Canidae
Kidney
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Dogs
Matrix Metalloproteinase 14
Biological Phenomena
Pathologic Processes
Caseins
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Kidney fibrosis
  • Matrilysin
  • Matrix metalloproteinase
  • Stromelysin-1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome. / Rao, Velidi H.; Lees, George E.; Kashtan, Clifford E.; Delimont, Duane C.; Singh, Rakesh K; Meehan, Daniel T.; Bhattacharya, Gautam; Berridge, Brian R.; Cosgrove, Dominic E.

In: Pediatric Nephrology, Vol. 20, No. 6, 01.06.2005, p. 732-739.

Research output: Contribution to journalArticle

Rao, VH, Lees, GE, Kashtan, CE, Delimont, DC, Singh, RK, Meehan, DT, Bhattacharya, G, Berridge, BR & Cosgrove, DE 2005, 'Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome', Pediatric Nephrology, vol. 20, no. 6, pp. 732-739. https://doi.org/10.1007/s00467-004-1805-5
Rao, Velidi H. ; Lees, George E. ; Kashtan, Clifford E. ; Delimont, Duane C. ; Singh, Rakesh K ; Meehan, Daniel T. ; Bhattacharya, Gautam ; Berridge, Brian R. ; Cosgrove, Dominic E. / Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome. In: Pediatric Nephrology. 2005 ; Vol. 20, No. 6. pp. 732-739.
@article{86d0c0f7576540ab9a4bf492812bf5bd,
title = "Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome",
abstract = "Matrix metalloproteinases (MMPs) play an important regulatory role in many biological and pathological processes and their specific role in Alport syndrome (AS) is not yet clearly defined. In this study, the naturally occurring canine X-linked AS was used to demonstrate a potential role for MMP-3 and MMP-7 in Alport renal pathogenesis. Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS. In the present study, we examined necropsy samples of renal cortex from normal and XLAS dogs for MMP-3 and MMP-7 as they have the potential to activate MMP-2 and MMP-9. Immunohistochemical analysis showed strong immunostaining for both MMP-3 and MMP-7 in the interstitial space of XLAS kidneys, while virtually no immunostaining was observed in similar fields from normal dogs. RT-PCR and casein zymography confirmed that both mRNA transcripts and activities of MMP-3 and MMP-7 are elevated in XLAS kidneys. The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS. Thus, these data further implicate a role for the MMPs in progressive renal pathogenesis associated with AS.",
keywords = "Kidney fibrosis, Matrilysin, Matrix metalloproteinase, Stromelysin-1",
author = "Rao, {Velidi H.} and Lees, {George E.} and Kashtan, {Clifford E.} and Delimont, {Duane C.} and Singh, {Rakesh K} and Meehan, {Daniel T.} and Gautam Bhattacharya and Berridge, {Brian R.} and Cosgrove, {Dominic E}",
year = "2005",
month = "6",
day = "1",
doi = "10.1007/s00467-004-1805-5",
language = "English (US)",
volume = "20",
pages = "732--739",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Dysregulation of renal MMP-3 and MMP-7 in canine X-linked Alport syndrome

AU - Rao, Velidi H.

AU - Lees, George E.

AU - Kashtan, Clifford E.

AU - Delimont, Duane C.

AU - Singh, Rakesh K

AU - Meehan, Daniel T.

AU - Bhattacharya, Gautam

AU - Berridge, Brian R.

AU - Cosgrove, Dominic E

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Matrix metalloproteinases (MMPs) play an important regulatory role in many biological and pathological processes and their specific role in Alport syndrome (AS) is not yet clearly defined. In this study, the naturally occurring canine X-linked AS was used to demonstrate a potential role for MMP-3 and MMP-7 in Alport renal pathogenesis. Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS. In the present study, we examined necropsy samples of renal cortex from normal and XLAS dogs for MMP-3 and MMP-7 as they have the potential to activate MMP-2 and MMP-9. Immunohistochemical analysis showed strong immunostaining for both MMP-3 and MMP-7 in the interstitial space of XLAS kidneys, while virtually no immunostaining was observed in similar fields from normal dogs. RT-PCR and casein zymography confirmed that both mRNA transcripts and activities of MMP-3 and MMP-7 are elevated in XLAS kidneys. The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS. Thus, these data further implicate a role for the MMPs in progressive renal pathogenesis associated with AS.

AB - Matrix metalloproteinases (MMPs) play an important regulatory role in many biological and pathological processes and their specific role in Alport syndrome (AS) is not yet clearly defined. In this study, the naturally occurring canine X-linked AS was used to demonstrate a potential role for MMP-3 and MMP-7 in Alport renal pathogenesis. Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS. In the present study, we examined necropsy samples of renal cortex from normal and XLAS dogs for MMP-3 and MMP-7 as they have the potential to activate MMP-2 and MMP-9. Immunohistochemical analysis showed strong immunostaining for both MMP-3 and MMP-7 in the interstitial space of XLAS kidneys, while virtually no immunostaining was observed in similar fields from normal dogs. RT-PCR and casein zymography confirmed that both mRNA transcripts and activities of MMP-3 and MMP-7 are elevated in XLAS kidneys. The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS. Thus, these data further implicate a role for the MMPs in progressive renal pathogenesis associated with AS.

KW - Kidney fibrosis

KW - Matrilysin

KW - Matrix metalloproteinase

KW - Stromelysin-1

UR - http://www.scopus.com/inward/record.url?scp=18644382127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18644382127&partnerID=8YFLogxK

U2 - 10.1007/s00467-004-1805-5

DO - 10.1007/s00467-004-1805-5

M3 - Article

VL - 20

SP - 732

EP - 739

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 6

ER -