Hirudin reduces the expression of markers of the extracellular matrix in renal tubular epithelial cells in a rat model of diabetic kidney disease
Mechanism study published in Medical Science Monitor (2020)
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-1alpha (HIF-1alpha), 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-1alpha, and VEGF were evaluated following knockdown or overexpression of HIF-1alpha. 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-1alpha, 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-1alpha group (P<0.05). Compared with the control group, the expression of ECM associated proteins was increased in the HIF-1alpha 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-1alpha/VEGF signaling pathway in DKD renal tubular epithelial cells.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Hirudin reduces extracellular-matrix marker expression in renal tubular epithelial cells in diabetic nephropathy rat model — anti-fibrotic mechanism extension.
Почему это важно для гирудотерапии
This study investigated the effects of hirudin on extracellular matrix (ECM) production in a rat model of diabetic kidney disease (DKD) and in cultured HK-2 human renal tubule epithelial cells. Hirudin significantly improved renal function in DKD rats and down-regulated fibronectin, type IV collagen, HIF-1alpha, and VEGF, with the authors concluding it reduced ECM markers by inhibiting the HIF-1alpha/VEGF signaling pathway. The relevance to ASH is indirect, as the abstract focuses on hirudin's pharmacological effects in DKD without mentioning leech saliva, hirudotherapy, or a leech-derived source. The main caveat is that findings are limited to an animal model and in vitro cell culture, with no human clinical data presented.
Цитирование
Hirudin reduces the expression of markers of the extracellular matrix in renal tubular epithelial cells in a rat model of diabetic kidney disease.
Pang X et al. · Medical science monitor, 2020
Связанный клинический контекст
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