Role of TRPV4 in matrix stiffness-induced expression of EMT-specific LncRNA.

Role of TRPV4 in matrix stiffness-induced expression of EMT-specific LncRNA.
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DOI:
10.1007/s11010-020-03844-1
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发表时间:
2020-11
影响因子:
4.3
通讯作者:
Rahaman SO
Rahaman SO
中科院分区:
生物学3区
文献类型:
--
作者:
Sharma S;Ma L;Rahaman SO

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长非编码RNA(LncRNAs)是一种长(200个碱基)、非编码的单链RNA,已成为基因表达、细胞分化、发育和肿瘤发生的主要调节因子。鉴于基质刚性在与这些过程相关的细胞功能中发挥作用的事实,重要的是要询问基质刚性在调节lncRNAs表达中起什么作用。在这篇报道中,我们发现:1)基质僵硬导致原代正常小鼠表皮角质形成细胞上皮-间充质转化相关的lncRNAs和mRNAs的差异表达;ii)转化生长因子β-1和基质僵硬的联合刺激导致上皮间充质转化相关的lncRNA和mRNAs的差异表达;以及iii)香草样细胞亚家族的瞬时受体电位通道TRPV4在转化生长因子β-1和基质僵硬的联合刺激下的差异表达中起作用。这些数据表明,TRPV4是一种候选的质膜机械传感器,可以传输对lncRNA表达至关重要的基质传感信号。我们的结果还表明,我们已经建立并验证了一个能够发现新的对基质硬化敏感的lncRNAs和mRNAs的检测系统。
Long non-coding RNAs (LncRNAs) are long (>200 bases), non-coding, single-stranded RNAs that have emerged as major regulators of gene expression, cell differentiation, development, and oncogenesis. In view of the fact that matrix stiffness plays a role in cellular functions associated with these processes, it is important to ask what role matrix stiffness plays in regulating expression of LncRNAs. In this report, we show that i) matrix stiffness causes differential expression of epithelial-mesenchymal transition (EMT)-related LncRNAs and mRNAs in primary mouse normal epidermal keratinocytes, ii) differential expression of EMT-related LncRNAs and mRNAs occurs in response to combined stimulation of transforming growth factor β1 and matrix stiffness, and iii) transient receptor potential (TRP) channel of the vanilloid subfamily, TRPV4, a matrix stiffness-sensitive ion channel, plays a role in differential expression of EMT-related LncRNAs and mRNAs in response to combined stimulation by TGFβ1 and matrix stiffness. These data identify TRPV4 as a candidate plasma membrane mechanosensor that transmits matrix-sensing signals essential to LncRNA expression. Our results also show that we have established and validated an assay system capable of discovering novel LncRNAs and mRNAs sensitive to matrix stiffening.
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