Advanced glycation end products decrease mesangial cell MMP-7: a role in matrix accumulation in diabetic nephropathy?
Kidney Int
; 72(4): 481-8, 2007 Aug.
Article
de En
| MEDLINE
| ID: mdl-17554258
ABSTRACT
Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-beta.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteur de croissance transformant bêta
/
Produits terminaux de glycation avancée
/
Matrix metalloproteinase 7
/
Diabète expérimental
/
Diabète de type 2
/
Néphropathies diabétiques
/
Cellules mésangiales
Type d'étude:
Etiology_studies
Langue:
En
Journal:
Kidney Int
Année:
2007
Type de document:
Article
Pays d'affiliation:
Australie