Escalada, F.J. (Francisco Javier)

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2020 - 20222

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    MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade
    (2020) Paramo, J.A. (José Antonio); Escalada, F.J. (Francisco Javier); Riera, M. (Marta); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Slon-Roblero, M.F. (María Fernanda); Soler, M.J. (María José)
    Matrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473±274pg/ml vs. 332±151; p=0.02) and TIMP-1 (573±296ng/ml vs. 375±317; p<0.001) levels were signifcantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to endstage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and signifcant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.
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    Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes
    (MDPI AG, 2022) Escalada, F.J. (Francisco Javier); Orbe, J. (Josune); Fernández-Seara, M.A. (María A.); Mora-Gutiérrez, J.M. (José María); Garcia-Fernandez, N. (Nuria); Dolcet-Negre, M.M. (Marta M.); Abasheva, D. (Daria)
    Background: Matrix metalloproteinase-10 (MMP-10) levels increase progressively starting from early diabetic kidney disease (DKD) stages. Vitamin D3 (vitD3 ) deficit is associated with a higher risk of diabetic microangiopathy. Reduced MMP-10 expression has been observed after exposure to vitD3 . Aim: to assess how vitD3 status is related to MMP-10 levels in patients with Type 2 diabetes (T2D). Methods: 256 patients with T2D were included in this cross-sectional study. Demographic, clinical and serum MMP-10 and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were collected from each patient. The association between MMP-10 and (25(OH)D3 ) levels was assessed using a correlation analysis and fitting a multivariate linear regression model. Results: Serum MMP-10 levels were inversely correlated with circulating 25(OH)D3 (rho = −0.25; p < 0.001). In the subgroup analysis this correlation was significant in patients with DKD (rho = −0.28; p = 0.001) and in subjects with vitD3 deficit (rho = −0.24; p = 0.005). In the regression model adjusted for kidney function, body adiposity, smoking and vitD supplementation MMP-10 levels were 68.7 pg/mL lower in patients with 25(OH)D3 > 20 ng/mL, with respect to ≤20 ng/mL (p = 0.006). Conclusions: vitD3 repletion status is an independent predictor of MMP-10 levels in T2D patients. Perhaps, high 25(OH)D3 values should be targeted in these patients in order to prevent vascular complications.