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骨化三醇和甲基强的松龙对体外微小病变肾病足细胞功能的影响。

The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.

机构信息

Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Jerzego Waszyngtona 13, 15-269, Białystok, Poland.

Ist Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Żurawia 14, 15-540, Białystok, Poland.

出版信息

Sci Rep. 2023 Aug 5;13(1):12731. doi: 10.1038/s41598-023-39893-x.

DOI:10.1038/s41598-023-39893-x
PMID:37543700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10404287/
Abstract

Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.

摘要

微小病变病(MCD)被认为是肾病综合征的主要病因之一,是一种伴有足细胞裂孔隔膜蛋白改变的复杂病理状态。许多研究表明维生素 D3 在维持正常肾小球功能方面起着重要作用。然而,关于该化合物对足细胞的直接潜在作用的数据却很少。因此,我们在这里评估了骨化三醇(活性维生素 D3)除了常用的类固醇(甲泼尼龙)以外,对足细胞功能的影响。我们使用 CIHP-1 足细胞系在体外建立了脂多糖-顺铂(LPS-PAN)诱导的 MCD 模型。使用流式细胞术、RT-PCR、共聚焦显微镜和 TEER 分析评估细胞活力、足细胞相关裂孔隔膜蛋白、形态和屏障功能。骨化三醇或甲泼尼龙对细胞活力没有影响。与先前报道的总肾小球变化相比,足细胞相关蛋白对体外治疗的反应不同。在测试化合物存在的情况下,足细胞形态得到部分恢复。此外,TEER 分析显示,当使用维生素 D3 或类固醇时,LPS-PAN 诱导的细胞作为屏障的功能得到改善。总之,报告了骨化三醇或选定类固醇对体外 MCD 模型足细胞的显著调节潜力。进一步研究维生素 D3 在伴随 MCD 的足细胞相关现象中的作用非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/1d1c8a4d6cbf/41598_2023_39893_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/2632dbe0677e/41598_2023_39893_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/f912df0fc14f/41598_2023_39893_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/b6542d725415/41598_2023_39893_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/bca3c58853b1/41598_2023_39893_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/1d1c8a4d6cbf/41598_2023_39893_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/2632dbe0677e/41598_2023_39893_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/f912df0fc14f/41598_2023_39893_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/b6542d725415/41598_2023_39893_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/bca3c58853b1/41598_2023_39893_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cb/10404287/1d1c8a4d6cbf/41598_2023_39893_Fig5_HTML.jpg

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本文引用的文献

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