Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability.
Diabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p < 0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31 microg/day; p < 0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.
Ishii
Hideto
H
Bioethics Research Centre, Tokyo Medical and Dental University, 1-5-45 Yushima, D-809, Bunkyo-ku, Tokyo 113-8519, Japan.
Hiraoka
Megumi
M
Tanaka
Akira
A
Shimokado
Kentaro
K
Yoshida
Masayuki
M
D000419:Albuminuria; D000818:Animals; D017306:Annexin A2 / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size; D011994:Recombinant Proteins; D019851:Thrombophilia / Q000188:drug therapy*
C472822:ANXA2 protein, human; D017306:Annexin A2; D011994:Recombinant Proteins