长链非编码 RNA TUG1 的过表达可减轻 TNF-α诱导的 Cajal 间质细胞炎症损伤。
Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal.
机构信息
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):312-320. doi: 10.26355/eurrev_201901_16778.
OBJECTIVE
Irritable bowel syndrome (IBS) is a common functional disorder in the gastrointestinal tract. Inflammatory response has been found to participate in the pathogenesis of IBS. This study aimed to explore the effects of long non-coding RNA taurine upregulated gene 1 (TUG1) on tumor necrosis factor alpha (TNF-α)-induced interstitial cells of Cajal (ICC) inflammatory injury, which was relevant to the pathogenesis of IBS.
PATIENTS AND METHODS
The expression levels of TUG1 and microRNA-127 (miR-127) were analyzed by qRT-PCR. Viability, apoptosis and the expression of apoptosis-associated factors were analyzed by CCK-8 assay, flow cytometry and Western blot, respectively. The mRNA and protein levels of pro-inflammatory cytokines were detected by qRT-PCR and Western blot, respectively. Finally, activations of nuclear factor kappa-B (NF-κB) and Notch pathways were evaluated by Western blot.
RESULTS
TNF-α treatment inhibited ICC viability, induced ICC apoptosis and promoted an inflammatory response in ICC. TUG1 was downregulated in TNF-α-treated ICC. TUG1 overexpression protected ICC from TNF-α-induced apoptosis and pro-inflammatory cytokines expression. TUG1 suppression showed opposite effects. MiR-127 was negatively regulated by TUG1 and implicated in the action of TUG1 in ICC. MiR-127 up-regulation largely reversed the effects of TUG1 on TNF-α-treated ICC. Mechanistically, TUG1 inhibited TNF-α-induced activation of NF-κB and Notch pathways in ICC by down-regulating miR-127.
CONCLUSIONS
TUG1 attenuated TNF-α-caused apoptosis and inflammatory response in ICC by down-regulating miR-127 and then inactivating NF-κB and Notch pathways.
目的
肠易激综合征（IBS）是一种常见的胃肠道功能障碍。炎症反应被发现参与了 IBS 的发病机制。本研究旨在探讨长链非编码 RNA 牛磺酸上调基因 1（TUG1）对肿瘤坏死因子-α（TNF-α）诱导的肠间质细胞（ICC）炎症损伤的影响，这与 IBS 的发病机制有关。
患者和方法
通过 qRT-PCR 分析 TUG1 和 microRNA-127（miR-127）的表达水平。通过 CCK-8 测定、流式细胞术和 Western blot 分别分析细胞活力、细胞凋亡和细胞凋亡相关因子的表达。通过 qRT-PCR 和 Western blot 检测促炎细胞因子的 mRNA 和蛋白水平。最后，通过 Western blot 评估核因子 kappa-B（NF-κB）和 Notch 通路的激活。
结果
TNF-α 处理抑制 ICC 活力，诱导 ICC 凋亡，并促进 ICC 的炎症反应。TUG1 在 TNF-α 处理的 ICC 中下调。TUG1 过表达可保护 ICC 免受 TNF-α 诱导的细胞凋亡和促炎细胞因子表达。TUG1 抑制则表现出相反的效果。miR-127 受 TUG1 负调控，并参与了 TUG1 在 ICC 中的作用。miR-127 的上调在很大程度上逆转了 TUG1 对 TNF-α 处理的 ICC 的作用。机制上，TUG1 通过下调 miR-127 抑制 TNF-α 诱导的 ICC 中 NF-κB 和 Notch 通路的激活。
结论
TUG1 通过下调 miR-127 抑制 TNF-α 引起的 ICC 凋亡和炎症反应，从而使 NF-κB 和 Notch 通路失活。
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