AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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 diabeticmouse 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 diabeticMmp10 −⁄− mice than in their Mmp10 +/+ counterparts. There were more kidney-infiltrating macrophages in diabeticMmp10+/+ mice, suggesting that MMP-10 contributes to the inflammatory response leading to microvascular complications. The loss of neuronal cells in the retinas of diabeticMmp10 +/+ mice was higher than in Mmp10 −⁄− mice. Retinal inflammation was decreased in Mmp10 −⁄− mice, as indicated by their reduced retinal caspase-1 levels. CONCLUSIONS/ INTERPRETATION: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.
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