Matrix metalloproteinase-10 plays an active role in microvascular complications in type 1 diabetic patients

Abstract

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. 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. 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. 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.