Dataset Information

Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells.

ABSTRACT:

Introduction

The prevalence of renal fibrosis is higher in older than in younger individuals. Through paracrine activity, bone marrow mesenchymal stem cell-derived microvesicles (BM-MSC-MVs) influence the process of renal fibrosis. Differences in microRNA (miRNA) expression of BM-MSC-MVs that correlate with the age of the subjects and the correlation between miRNA expression and the process of renal fibrosis have not been established. The present study aimed to analyze differences in miRNA expression of BM-MSC-MVs between young or older rats and its influence on tumor growth factor-beta 1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) of HK2 cells to explore the causes of renal fibrosis in aged tissues.

Methods

miRCURY LNA Array (version 18.0) was used to identify differentially expressed miRNAs in BM-MSC-MVs of 3- and 24-month-old Fisher344 rats. Reverse transcription-polymerase chain reaction was used to verify miRNA levels in BM-MSC-MVs and in the serum of rats. A TGF-β1-mediated EMT model was used to study the effects of BM-MSC-MVs and differentially expressed miRNAs on EMT.

Results

BM-MSCs from older rats showed more severe aging phenotypes compared with those of young rats. In addition, the growth rate and cell migration of BM-MSCs derived from older rats were significantly reduced. In secreted BM-MSC-MVs, the expression of miR-344a, miR-133b-3p, miR-294, miR-423-3p, and miR-872-3p was significantly downregulated in older rats than in younger rats (P < 0.05), and the serum level of these miRNAs exhibited the same patterns. Intervention using BM-MSC-MVs resulted in the weakening of TGF-β1-mediated EMT in the aged rats. MiR-344a, miR-133b-3p, and miR-294 affected TGF-β1-mediated EMT in HK2 cells. Among these, miR-133b-3p and miR-294 significantly inhibited TGF-β1-mediated EMT in HK2 cells (P < 0.05).

Conclusions

In older rats, the inhibitory effect of BM-MSC-MVs on TGF-β1-mediated HK2 cell EMT was weaker than that observed in younger rats. In addition, miR-133b-3p and miR-294, which were downregulated in BM-MSC-MVs of older rats, remarkably inhibited TGF-β1-mediated EMT in HK2 cells, suggesting that these may play a role in the fibrosis of aging renal tissues.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4587922 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells.

Wang Yan Y Fu Bo B Sun Xuefeng X Li Diangeng D Huang Qi Q Zhao Weihong W Chen Xiangmei X

Stem cell research & therapy 20150928

<h4>Introduction</h4>The prevalence of renal fibrosis is higher in older than in younger individuals. Through paracrine activity, bone marrow mesenchymal stem cell-derived microvesicles (BM-MSC-MVs) influence the process of renal fibrosis. Differences in microRNA (miRNA) expression of BM-MSC-MVs that correlate with the age of the subjects and the correlation between miRNA expression and the process of renal fibrosis have not been established. The present study aimed to analyze differences in miR ...[more]

PMID: 26415502

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Project description:BackgroundMesenchymal stem cells derived from human tissues have been widely used for tissue regeneration because of their strong self-renewal capacity and multi-potential properties. Autophagy plays a vital role in maintaining bone homeostasis. However, the mechanism underlying this role for autophagy in the osteogenic differentiation of mesenchymal stem cells remains to be elucidated.MethodsTwo microarray datasets were downloaded from the GEO database. Fourteen bone marrow mesenchymal stem cell samples comprising control and induction groups were selected to identify differentially expressed autophagy-related genes via multiple bioinformatics approaches, followed by functional analysis. Interactions among differentially expressed autophagy genes, miRNAs, and transcription factors were analyzed and visualized using Cytoscape software. The association between hub differentially expressed genes and autophagy was validated by qRT-PCR.ResultsTen autophagy-related genes (including VPS8, NDRG4, and CYBB) were identified as osteogenic hub genes. Correlation analysis revealed that CYBB was highly correlated with the sensitivity to multiple drugs, such as imexon, megestrol acetate, and isotretinoin. The regulatory network displayed a complex connection among miRNAs, transcription factors, and differentially expressed autophagy genes. Friends' analysis showed that NDRG4 was highly closely related to other hub genes (P < 0.05). Furthermore, NDRG4 expression was downregulated in the induction group (P < 0.01). NDRG4 was significantly correlated with infiltrating immune cells, including monocytes, eosinophils, type 17 T helper cells, neutrophils, activated CD8 T cells, and immature B cells. Levels of the 10 autophagy-related genes (including VPS8, NDRG4, and CYBB) were successfully validated based on in vitro experiments.ConclusionWe identified candidate molecules to further investigate their functions in osteogenesis, providing novel insights into the role of autophagy in mesenchymal stem cell differentiation.

Dataset Information

Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells.

Introduction

Methods

Results

Conclusions

Publications

Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells.

Similar Datasets

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