miR-10396b-3p inhibits mechanical stress-induced ligamentum flavum hypertrophy by targeting IL-11
miR-10396b-3p inhibits mechanical stress-induced ligamentum flavum hypertrophy by targeting IL-11
复制标题
miR-10396b-3p 通过靶向 IL-11 抑制机械应力诱导的黄韧带肥大
DOI：
10.1096/fj.202100169rr
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发表时间：
2021-06-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Liang
中科院分区：
文献类型：
--
作者：
Li, Peng;Liu, Chunlei;Wang, Liang
黄韧带肥大（LFH）导致腰椎管狭窄（LSS），由LF组织炎症和纤维化引起。新出现的证据表明，失调的microRNAs（miRNAs）在炎症和纤维化中具有重要作用。机械应力（MS）已被探索为LFH病理学进展的起始步骤;机械应力后诱导的炎症相关miRNA与纤维化病理学有关。然而，MS‐miRNAs‐LFH的病理生理机制仍有待阐明。使用miRNAs测序分析和随后的qRT-PCR测定确认，我们确定了miR-10396 b-3 p表达降低和IL-11（白细胞介素-11）表达增加是肥大LF组织中LSS发展的反应。我们还发现IL-11与I型胶原和III型胶原的纤维化指标呈正相关。在体外，miR-10396 b-3 p的上调显著降低了IL-11的表达水平，而miR-10396 b-3 p的下调增加了IL-11的表达。荧光素酶报告基因分析表明IL-11是miR-10396 b-3 p的直接靶点。此外，循环机械应力在体外抑制miR-10396 b-3 p并诱导IL-11、胶原蛋白I和胶原蛋白III。我们的结果表明，miR-10396 b-3 p的过表达通过抑制IL-11抑制胶原I和III来抑制MS诱导的LFH。这些数据表明，MS-miR-10396 b-3 p-IL-11轴在LFH的病理进展中起关键作用。
Ligamentum flavum hypertrophy (LFH) leads to lumbar spinal stenosis (LSS) caused by LF tissue inflammation and fibrosis. Emerging evidence has indicated that dysregulated microRNAs (miRNAs) have an important role in inflammation and fibrosis. Mechanical stress (MS) has been explored as an initiating step in LFH pathology progression; the inflammation‐related miRNAs induced after mechanical stress have been implicated in fibrosis pathology. However, the pathophysiological mechanism of MS‐miRNAs‐LFH remains to be elucidated. Using miRNAs sequencing analysis and subsequent confirmation with qRT‐PCR assays, we identified the decreased expression of miR‐10396b‐3p and increased expression of IL‐11 (interleukin‐11) as responses to the development of LSS in hypertrophied LF tissues. We also found that IL‐11 is positively correlated with fibrosis indicators of collagen I and collagen III. The up‐regulation of miR‐10396b‐3p significantly decreased the level of IL‐11 expression, whereas miR‐10396b‐3p down‐regulation increased IL‐11 expression in vitro. Luciferase reporter assay indicates that IL‐11 is a direct target of miR‐10396b‐3p. Furthermore, cyclic mechanical stress inhibits miR‐10396b‐3p and induces IL‐11, collagen I, and collagen III in vitro. Our results showed that overexpression of miR‐10396b‐3p suppresses MS‐induced LFH by inhibiting collagen I and III via the inhibition of IL‐11. These data suggest that the MS‐miR‐10396b‐3p‐IL‐11 axis plays a key role in the pathological progression of LFH.