Matrix metalloproteinase-10 plays an active role in microvascular complications in type 1 diabetic patients.
OBJECTIVE
The role of metalloproteinase-10 (MMP-10) in type 1 diabetes is not known. We hypothesise that it plays a role in the onset and progression of diabetic nephropathy and retinopathy.


METHODS
Serum MMP-10 levels from 269 patients with type 1 diabetes were measured, and their association with microvascular complications was analysed. We also studied whether knocking out the Mmp10 gene influenced the extent of renal injury and retinal damage in a streptozotocin-induced diabetic mouse model.


RESULTS
The risk of nephropathy and proliferative retinopathy associated with the highest vs the lowest MMP-10 tertile was increased three to four times independently of the classical risk factors. Accordingly, renal function and morphology were better preserved in diabetic Mmp10 −⁄− mice than in their Mmp10 +/+ counterparts. There were more kidney-infiltrating macrophages in diabetic Mmp10+/+ mice, suggesting that MMP-10 contributes to the inflammatory response leading to microvascular complications. The loss of neuronal cells in the retinas of diabetic Mmp10 +/+ mice was higher than in Mmp10 −⁄− mice. Retinal inflammation was decreased in Mmp10 −⁄− mice, as indicated by their reduced retinal caspase-1 levels.


CONCLUSIONS
MMP-10 is involved in the development of microvascular complications in type 1 diabetes and emerges as a potential therapeutic target for slowing down the evolution of diabetic nephropathy and retinopathy.
Marta
M
Toni
José
J
Hermida
María J
MJ
Goñi
Patricia
P
Fernández
William C
WC
Parks
Estefanía
E
Toledo
Ramón
R
Montes
Nieves
N
Díez
D000328:Adult; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000201:enzymology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology; D007677:Kidney Function Tests; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012160:Retina / Q000201:enzymology; D013311:Streptozocin
D013311:Streptozocin; D053506:Matrix Metalloproteinase 10; D020780:Matrix Metalloproteinase 9