Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability

Hideto Ishii; Megumi Hiraoka; Akira Tanaka; Kentaro Shimokado; Masayuki Yoshida

doi:10.1160/TH06-07-0381

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(01): 124-128
DOI: 10.1160/TH06-07-0381

Animal Models

Schattauer GmbH

Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability

Hideto Ishii

¹Bioethics Research Centre, Tokyo Medical and Dental University, Tokyo, Japan

²Department of Geriatrics and Vascular Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

,

Megumi Hiraoka

³Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

,

Akira Tanaka

⁴Kanto Gakuin University, Kanagawa, Japan

,

Kentaro Shimokado

²Department of Geriatrics and Vascular Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

,

Masayuki Yoshida

¹Bioethics Research Centre, Tokyo Medical and Dental University, Tokyo, Japan

²Department of Geriatrics and Vascular Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

³Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

› Author Affiliations

Abstract

Summary

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 µg/day; PBS, 1.55+/-0.31 µg/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.

Keywords

Annexins - hypercoagulability - endothelial cells - diabetes mellitus

Full Text

References

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