Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0920646 (
renal ischemia
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We examined the effect of
meprin A
, the major matrix degrading metalloproteinase in rat kidney, on the laminin-nidogen complex. N-terminal sequence information from the most abundant 55 kDa fragment revealed that it was a breakdown product of nidogen rather than laminin. In comparison with over 50 nidogen cleavage sites produced by other proteases, the
meprin A
-induced nidogen cleavage site at amino acid position 899-900, a glutamine-glycine site in the G3 domain, is unique. In addition, these data demonstrate that
meprin A
degrades the G3 domain of nidogen even in the presence of laminin binding, which usually accords protection from proteolytic degradation. Meprin A also degraded purified nidogen into similar breakdown products. Given that the tubular basement membrane is located on the basilar side of the cell, the location of
meprin A
on the apical brush border makes it difficult to envision a role for
meprin A
in injury-induced basement membrane component breakdown. Thus, we examined the possibility that following renal tubular epithelial cell injury,
meprin A
undergoes a translocation to reach the underlying basement membrane. After
renal ischemia
-reperfusion there was a marked alteration in
meprin A
staining with
meprin A
now distributed throughout the renal tubular cell cytoplasm and directly adherent to the tubular basement membrane. This was in contrast to the usual linear staining of the brush border of tubules in the corticomedullary junction. These data provide unequivocal evidence that following injury,
meprin A
undergoes redistribution and/or adherence to the tubular basement membrane. Since in our in vitro studies, we identified a distinct
meprin
-induced 55 kDa nidogen breakdown product, the urine was also examined for the presence of nidogen degradation products after rat
renal ischemia
-reperfusion injury. Western blots showed a marked increase in the urinary 55 kDa nidogen fragment as early as the first day following ischemia-reperfusion injury and continuing for six days. Taken together, these in vivo data strongly support the notion that the nidogen breakdown products are the result of partial degradation of tubular basement membrane by
meprin A
following renal tubular ischemia-reperfusion injury.
...
PMID:Meprin A, the major matrix degrading enzyme in renal tubules, produces a novel nidogen fragment in vitro and in vivo. 960 99
