Identification of miR-27b as a Novel Signature from the mRNA Profiles of Adipose-Derived Mesenchymal Stem Cells Involved in the Tolerogenic Response

被引：21

作者：

Chen, Kuang-Den ^{[1
,2
,3
]}

Goto, Shigeru ^{[1
,2
,3
,4
]}

Hsu, Li-Wen ^{[1
,2
,3
,5
]}

Lin, Tzu-Yang ^{[1
,2
,3
]}

Nakano, Toshiaki ^{[1
,2
,3
,6
,7
]}

Lai, Chia-Yun ^{[1
,2
,3
]}

Chang, Yen-Chen ^{[1
,2
,3
]}

Weng, Wei-Teng

Kuo, Yur-Ren ^{[7
,8
]}

Wang, Chih-Chi ^{[1
,2
,3
]}

Cheng, Yu-Fan ^{[7
,9
]}

Ma, Yen-Ying ^{[7
,10
]}

Lin, Chih-Che ^{[1
,2
,3
]}

Chen, Chao-Long ^{[1
,2
,3
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Liver Transplantat Program, Kaohsiung, Taiwan

[2] Kaohsiung Chang Gung Mem Hosp, Dept Surg, Kaohsiung, Taiwan

[3] Chang Gung Univ, Coll Med, Dept Surg, Kaohsiung, Taiwan

[4] Iwao Hosp, Yufuin, Japan

[5] Natl Cheng Kung Univ, Dept Chem, Tainan 70101, Taiwan

[6] Kaohsiung Chang Gung Mem Hosp, Grad Inst Clin Med Sci, Kaohsiung, Taiwan

[7] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Kaohsiung, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Diagnost Radiol, Kaohsiung, Taiwan

[10] Kaohsiung Chang Gung Mem Hosp, Dept Obstet & Gynecol, Kaohsiung, Taiwan

来源：

PLOS ONE | 2013年 / 8卷 / 04期

关键词：

FACTOR-I; STROMAL CELLS; HOMING FACTOR; LIVER; TISSUE; SDF-1; FACTOR-1-ALPHA; MOBILIZATION; SDF-1-ALPHA; REGULATORS;

D O I：

10.1371/journal.pone.0060492

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Adipose-derived mesenchymal stem cells (adipose-derived MSCs, ASCs) possess the ability to differentiate into multiple tissue types and have immune-modulatory properties similar to those of MSCs from other origins. However, the regulation of the MSC-elicited immune-modulatory activity by specific microRNA (miRNA) mechanisms remains unexplored. Gene expression profiling with knowledge-based functional enrichment analysis is an appropriate approach for unraveling these mechanisms. This tool can be used to examine the transcripts and miRNA regulators that differentiate the rat tolerogenic orthotopic liver transplantation (OLT; DA liver into PVG) and rejection OLT (DA liver into LEW) models. In both models, the rejection reaction was observed on postoperative day 7 similar to 14 (rejection phase) but was overcome only by the PVG recipients. Thus, the global gene expression patterns of ASCs from spontaneously tolerant (PVG) and acute rejecting (LEW) rats in response to LPS activation were compared. In this study, we performed miRNA enrichment analysis based on the analysis of pathway, gene ontology (GO) terms and transcription factor binding site (TFBS) motif annotations. We found that the top candidate, miR-27, was specifically enriched and had the highest predicted frequency. We also identified a greater than 3-fold increase of miR-27b expression in the ASCs of tolerant recipients (DA to PVG) compared to those of rejecting recipients (DA to LEW) during the rejection phase in the rat OLT model. Furthermore, our data showed that miR-27b knockdown has a positive influence on the allosuppressive activity that inhibits T-cell proliferation. We found that miR-27 knockdown significantly induced the expression of CXCL12 in cultured ASCs and the expression of CXCL12 was responsible for the miR-27b antagomir-mediated inhibition of T-cell proliferation. These results, which through a series of comprehensive miRNA enrichment analyses, might be relevant for stem cell-based therapeutic applications in immunosuppressive function using ASCs.

引用

页数：14

共 44 条

[1]

Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis [J].