30 May 2020 : Laboratory Research
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
Xinxin Pang1AG, Yage Zhang2CE, Xiujie Shi2B, Zining Peng2B, Yufeng Xing2CF, Han Jiarui2DG*DOI: 10.12659/MSM.921894
Med Sci Monit 2020; 26:e921894
Abstract
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 AND 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.
Keywords: Extracellular Matrix, Hirudins, Hypoxia-Inducible Factor 1, Vascular Endothelial Growth Factors, Hypoxia-Inducible Factor 1, alpha Subunit, Kidney Tubules, RNA, Messenger, Real-Time Polymerase Chain Reaction, Vascular Endothelial Growth Factor A
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