Effects of high glucose and thiamine on the balance between matrix metalloproteinases and their tissue inhibitors in vascular cells.
Pericyte survival in diabetic retinopathy depends also on interactions with extracellular matrix (ECM) proteins, which are degraded by matrix metalloproteinases (MMP). Elevated glucose influences ECM turnover, through expression of MMP and their tissue inhibitors, TIMP. We reported on reduced pericyte adhesion to high glucose-conditioned ECM and correction by thiamine. We aimed at verifying the effects of thiamine and benfotiamine on MMP-2, MMP-9 and TIMP expression and activity in human vascular cells with high glucose. In HRP, MMP-2 activity, though not expression, increased with high glucose and decreased with thiamine and benfotiamine; TIMP-1 expression increased with high glucose plus thiamine and benfotiamine; MMP-9 was not expressed. In EC, MMP-9 and MMP-2 expression and activity increased with high glucose, but thiamine and benfotiamine had no effects; TIMP-1 expression was unchanged. Neither glucose nor thiamine modified TIMP-2 and TIMP-3 expression. TIMP-1 concentrations did not change in either HRP or EC. High glucose imbalances MMP/TIMP regulation, leading to increased ECM turnover. Thiamine and benfotiamine correct the increase in MMP-2 activity due to high glucose in HRP, while increasing TIMP-1.
Tarallo
Sonia
S
Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy. sonia.tarallo@unito.it
Beltramo
Elena
E
Berrone
Elena
E
Dentelli
Patrizia
P
Porta
Massimo
M
D002478:Cells, Cultured; D017931:DNA Primers; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000201:enzymology; D013831:Thiamine / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005947:Glucose; D013831:Thiamine