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Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4

Kameswaran Surendran1, Theodore C Simon, Helen Liapis

  • 1Department of Pediatrics, Division of Biology and Biomedical Sciences, Washington University School of Medicine, and Saint Louis Children's Hospital, Missouri 63110, USA.

Kidney International
|May 20, 2004
PubMed
Abstract

Insights

Matrilysin, a protein involved in tissue repair, is newly found in damaged human and mouse kidneys. Its expression correlates with kidney disease progression and may be regulated by Wnt4 signaling.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Matrilysin is a matrix metalloproteinase involved in epithelial repair and host defense.
  • Its role in renal injury has not been previously described.

Purpose of the Study:

  • To investigate the expression and role of matrilysin in renal injury and fibrosis.
  • To determine the relationship between matrilysin and Wnt4 signaling in kidney disease.

Main Methods:

  • Immunohistochemistry on human kidney specimens and experimental mouse models.
  • Northern blotting and RNase protection assays (RPA) to assess gene expression.
  • In situ hybridization to determine the spatial relationship with Wnt4.

Main Results:

  • Matrilysin was absent in normal renal tubules but detected in various human kidney diseases (polycystic kidney disease, hydronephrosis).
  • Matrilysin expression was induced in mouse models of acute kidney injury and tubulointerstitial fibrosis.
  • Matrilysin localization in distal tubules/collecting ducts and its expression pattern paralleled Wnt4 during fibrosis progression.

Conclusions:

  • Matrilysin likely plays a role in renal tubular injury and the progression of tubulointerstitial fibrosis.
  • Wnt4 signaling may regulate matrilysin expression in the context of kidney disease.

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