State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin, China.
Cytotherapy. 2013 Dec;15(12):1511-6. doi: 10.1016/j.jcyt.2013.06.007. Epub 2013 Sep 10.
Toll-like receptors (TLRs) are expressed in human umbilical cord-derived mesenchymal stromal cells (UC-MSCs), and activation of TLRs plays an important role in proliferation, differentiation and immunoregulatory activity of UC-MSCs. We investigated whether TLRs regulated the expression of microRNAs (miRNAs) in UC-MSCs and the role of miRNAs.
With miRNA microarray analysis, we demonstrated that the expression of many miRNAs varied when UC-MSCs were stimulated with the ligand of toll-like receptor 4 (TLR4), lipopolysaccharide (LPS). The expression of some miRNAs was verified by polymerase chain reaction. It was found that microRNA-301a (miR-301a) was up-regulated by the ligands of TLR3 and TLR4, LPS and polyinosinic acid:polycytidylic acid poly(I:C). However, the inhibitors of nuclear factor κB NF-κB and interferon regulatory factor 3 IRF3 signal attenuated the effect of LPS and poly(I:C) on miR-301a expression. Over-expression or lower expression of miR-301a affected the cytokine secretion of UC-MSCs.
The expression of miR-301a in UC-MSCs was regulated by TLRs, and miR-301a affected the cytokine secretion of UC-MSCs.
Toll 样受体（TLRs）在人脐带间充质基质细胞（UC-MSCs）中表达，TLRs 的激活在 UC-MSCs 的增殖、分化和免疫调节活性中发挥重要作用。我们研究了 TLR 是否调节 UC-MSCs 中 microRNAs（miRNAs）的表达以及 miRNAs 的作用。
通过 miRNA 微阵列分析，我们证明了当 UC-MSCs 受到 TLR4 配体（脂多糖，LPS）刺激时，许多 miRNAs 的表达发生变化。通过聚合酶链反应验证了某些 miRNAs 的表达。发现 microRNA-301a（miR-301a）被 TLR3 和 TLR4 的配体、LPS 和多聚肌苷酸：多聚胞苷酸 poly(I:C)上调。然而，核因子κB NF-κB 和干扰素调节因子 3 IRF3 信号的抑制剂减弱了 LPS 和 poly(I:C)对 miR-301a 表达的影响。miR-301a 的过表达或低表达影响 UC-MSCs 的细胞因子分泌。
UC-MSCs 中 miR-301a 的表达受 TLR 调节，miR-301a 影响 UC-MSCs 的细胞因子分泌。
