Hirudin Reduces the Expression of Markers of the Extracellular Matrix in Renal Tubular Epithelial Cells in a Rat Model of Diabetic Kidney Disease Through the Hypoxia-Inducible Factor-1α (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway

BACKGROUND: This study aimed to investigate the effects of hirudin on the production of extracellular matrix (ECM) factors by renal tubular epithelial cells in a rat model of diabetic kidney disease (DKD) and HK-2 human renal tubule epithelial cells. MATERIAL/METHODS: Sprague-Dawley rats were divided into the normal control group (n=10), the normal control+hirudin group (n=10), the DKD model group (n=12) and the DKD+hirudin group (n=12). At the end of the study, renal histopathology was undertaken, and the expression of type IV collagen, fibronectin, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). HK-2 cells were cultured in glucose and treated with hirudin. Protein and mRNA expression of fibronectin, type IV collagen, HIF-1α, and VEGF were evaluated following knockdown or overexpression of HIF-1α. RESULTS: Hirudin significantly improved renal function in the rat model of DKD (P<0.01), and significantly down-regulated the expression of fibronectin, type IV collagen, HIF-1α, and VEGF proteins (P<0.05). The expression of ECM associated proteins was increased in HK-2 cells treated with high glucose and reduced in the high glucose+shRNA HIF-1α group (P<0.05). Compared with the control group, the expression of ECM associated proteins was increased in the HIF-1α over-expressed group, and decreased following treatment with hirudin (P<0.05). CONCLUSIONS: Hirudin reduced the expression of markers of ECM by inhibiting the HIF-1α/VEGF signaling pathway in DKD renal tubular epithelial cells.