Suppression of Mesangial Cell Proliferation and Extracellular Matrix Production in Streptozotocin-Induced Diabetic Mice by Adiponectin In Vitro and In Vivo

Abstract

Renal growth, particularly hypertrophy, is a feature of diabetic nephropathy (DN). Adiponectin, an adipocyte-derived hormone, is an important regulator of cell proliferation. Recent studies have suggested that adiponectin has a protective effect in the kidney. The purpose of this study was to investigate the therapeutic effects and the underlying mechanisms of adiponectin in early DN. Mouse mesangial cells (MMCs) were cultured in media containing different concentrations of platelet-derived growth factor-BB (PDGF-BB) with or without adiponectin. MMC proliferation and expression of type IV collagen, laminin, and fibronectin were investigated. Streptozotocin-induced diabetic mice were injected intravenously with recombinant lentivirus encoding the mouse adiponectin gene (Lenti-Acdc-IRES-EGFP). Urinary microalbumin, serum adiponectin level, and expression of proliferating cell nuclear antigen, type IV collagen, laminin, and fibronectin were determined. Adiponectin inhibited the increases in MMC proliferation and expression of type IV collagen, laminin, and fibronectin induced by PDGF-BB. Adiponectin also effectively reduced renal cell proliferation and expression of type IV collagen, laminin, and fibronectin when it was introduced in vivo by lentivirus-mediated gene transfer. These findings suggest that adiponectin exerts renoprotective effects by inhibiting renal cell proliferation and reducing synthesis of extracellular matrix proteins, thus suppressing the development and progression of DN.

Key words

adiponectin - diabetic nephropathy - lentivirus - extracellular matrix proteins

^* These authors contributed equally to this work and should be considered as co-first authors.

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