Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011881 (
diabetic nephropathy
)
10,836
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We investigated
pregnancy-associated plasma protein-A
(
PAPP-A
) in
diabetic nephropathy
. Normal human kidney showed specific staining for
PAPP-A
in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of
PAPP-A
in the development of
diabetic nephropathy
, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated
PAPP-A
expression in glomeruli is associated with
diabetic nephropathy
in humans and absence of
PAPP-A
is associated with resistance to the development of indicators of
diabetic nephropathy
in mice. These data suggest
PAPP-A
as a potential therapeutic target for
diabetic nephropathy
.
...
PMID:Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy. 2388 37
