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首页> 外文期刊>Translational research: the journal of laboratory and clinical medicine >Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis
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Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis

机译：精确切割的人类肾脏切片作为阐明肾脏纤维化过程的模型

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摘要

Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor beta 1 (TGF-beta 1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-beta 1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and alpha-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.
机译：慢性肾脏疾病是一个主要的健康问题，目前缺乏弥合动物研究与临床研究之间差距的实验模型。在这里，我们评估了精确切肾切片（PCKSs）作为肾脏疾病的潜在模型。从得自肿瘤肾切除术的人皮质组织制备PCKS，并培养长达96小时。确定形态，细胞活力和代谢功能（即尿苷5'-二磷酸-葡萄糖醛糖基转移酶和转运蛋白活性）以评估PCKS的完整性。此外，表征了炎症和纤维化相关的基因表达。最后，为验证模型，使用转化生长因子β1（TGF-β1）诱导了肾纤维化。 PCKSs的制备引起炎性组织反应，而长期孵育（96小时）则诱导纤维化，如1A1型胶原蛋白（COL1A1）和纤连蛋白1（FN1）表达的增加所表明。重要的是，PCKSs可以保持功能超过48小时，这可以通过积极的葡萄糖醛酸化和苯酚磺酞的摄取来证明。此外，细胞多样性似乎得以维持，但我们观察到肾素信使RNA水平明显下降，这表明我们的模型可能不适合研究足细胞在肾脏病理中的作用。此外，TGF-β1暴露会加剧纤维化，如多种纤维化标记物（包括COL1A1，FN1和α平滑肌肌动蛋白）表达增加所说明。总之，PCKSs在培养过程中保持其肾脏表型，似乎是研究肾脏疾病（例如肾纤维化）的有前途的模型。此外，PCKS的人类起源使该模型非常适合翻译研究。

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