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间充质干细胞移植可恢复 SLE 小鼠模型中狼疮疾病相关 miRNA 表达和 Th1/Th2 比值。

Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE.

机构信息

Laboratory Animal Research Center, Samsung Biomedical Research Institute, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea.

School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea.

出版信息

Sci Rep. 2016 Dec 7;6:38237. doi: 10.1038/srep38237.

DOI:10.1038/srep38237
PMID:27924862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5141468/
Abstract

C3.MRL-Fas/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Fas/J mice using a murine SLE model. C3.MRL-Fas/J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared. The Y group showed the greatest improvement in disease parameters, but with damaged trabecular integrity. ASC transplantation reduced anti-dsDNA levels, glomerular C3 deposition and CD138 proportion significantly, without trabecular damage. Furthermore, both cyclophosphamide and ASC treatment significantly decreased the ratio of Th1/Th2 compared with the saline-treatment. The expression levels of miR-31-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-379-5p were significantly higher, while those of miR150-5p were significantly lower in the C group than in the N group. The expression levels of miR-96-5p, miR-182-5p in the Y and H groups were significantly lower than in the C group. Thus, treatment with cyclophosphamide or ASC can change miRNAs and decrease miR-96-5p and miR-182-5p expression, as well as decreasing the CD138 proportion and the Th1/Th2 ratio, which might be involved in the therapeutic mechanism.

摘要

C3.MRL-Fas/J 小鼠自发产生高滴度的抗 dsDNA、轻度肾小球肾炎和严重的淋巴增生症状。本研究旨在比较长期连续给予人脂肪组织来源间充质干细胞(ASCs)和环磷酰胺治疗在 MRL-Fas/J 小鼠狼疮模型中的作用。将 C3.MRL-Fas/J 小鼠分为盐水(C)、环磷酰胺(Y)和 ASC(H)治疗组。还比较了用盐水(N)治疗的背景匹配对照 C3H 小鼠。Y 组的疾病参数改善最大,但小梁完整性受损。ASC 移植可显著降低抗 dsDNA 水平、肾小球 C3 沉积和 CD138 比例,而不会损害小梁。此外,与盐水治疗相比,环磷酰胺和 ASC 治疗均显著降低了 Th1/Th2 比值。与 N 组相比,C 组 miR-31-5p、miR-96-5p、miR-182-5p、miR-183-5p 和 miR-379-5p 的表达水平明显升高,而 miR150-5p 的表达水平明显降低。Y 组和 H 组的 miR-96-5p、miR-182-5p 表达水平明显低于 C 组。因此,环磷酰胺或 ASC 的治疗可以改变 miRNA,降低 miR-96-5p 和 miR-182-5p 的表达,并降低 CD138 比例和 Th1/Th2 比值,这可能涉及治疗机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/be95d305d8fd/srep38237-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/fd4a447b5e03/srep38237-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/f064a7d00cd0/srep38237-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/ea0e37c421ff/srep38237-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/8c5972fd72b1/srep38237-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/019e6809a2dc/srep38237-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/be95d305d8fd/srep38237-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/fd4a447b5e03/srep38237-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/f064a7d00cd0/srep38237-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/ea0e37c421ff/srep38237-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/8c5972fd72b1/srep38237-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/019e6809a2dc/srep38237-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbbb/5141468/be95d305d8fd/srep38237-f7.jpg

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