Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4.
BACKGROUND
Matrilysin, a secreted matrix metalloproteinase and target gene of Wnt signaling, functions in epithelial repair and host defense, but no role in renal injury has been described.


METHODS
Matrilysin expression was assessed in human kidney specimens by immunohistochemistry, and in experimental renal injury in mice by immunohistochemistry, Northern blotting, and RNase protection assays (RPA). A relationship to Wnt4, which is also induced in renal injury, was determined by RPA and in situ hybridization.


RESULTS
Matrilysin was not detected in the normal human renal tubular epithelium by immunohistochemistry. However, prominent staining was detected in sections from autosomal-dominant polycystic kidney disease in the cyst lining epithelium, atrophic tubules, and cyst micropolyps, and from hydronephrosis in dilated and atrophic tubules. Matrilysin expression was also induced by acute folic acid nephropathy and unilateral ureteral obstruction (UUO) in the mouse, and expression increased as acute injury progressed to tubulointerstitial fibrosis. Matrilysin staining was primarily localized to epithelium of distal tubule/collecting duct origin in both human and murine renal disease. Wnt signaling can induce matrilysin expression, and we found that the pattern of matrilysin expression during progression of renal fibrosis in the mouse after UUO or folic acid nephropathy, and in the jck model of murine polycystic kidney disease, closely paralleled that of Wnt4.


CONCLUSIONS
These observations suggest that matrilysin may have a role in renal tubular injury and progression of tubulointerstitial fibrosis, and that Wnt4 may regulate matrilysin expression in the kidney.
Surendran
Kameswaran
K
Department of Pediatrics, Division of Biology and Biomedical Sciences, Washington University School of Medicine, and Saint Louis Children's Hospital, Missouri 63110, USA.
Simon
Theodore C
TC
Liapis
Helen
H
McGuire
John K
JK
D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000235:genetics; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007684:Kidney Tubules / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D060528:Wnt4 Protein
D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D020783:Matrix Metalloproteinase 7