College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China.
J Hazard Mater. 2021 Mar 15;406:124682. doi: 10.1016/j.jhazmat.2020.124682. Epub 2020 Nov 26.
Hydrogen sulfide (HS) is an air pollutant, having toxic effects on immune system. Necroptosis has been discussed as a new form of cell death and plays an important role in inflammation. To investigate the mechanism of HS-induced immune injury, and the role of microRNAs (miRNAs) in this process, based on the results of high-throughput sequencing, we selected the most significantly changed miR-15b-5p for subsequent experiments. We further predicted and determined the targeting relationship between miR-15b-5p and TGFBR3 in HD11 through miRDB, Targetscan and dual-luciferase, and found that miR-15b-5p is highly expressed in HS-induced necroptosis and inflammation. To understand whether miR-15b-5p/TGFBR3 axis could involve in the process of necroptosis and inflammation, we further revealed that the high expression of miR-15b-5p and the knockdown of TGFBR3 can induce necroptosis. Nec-1 treatment enhanced the survival rate of cells. Notably, HS exposure induces oxidative stress and activates the TGF-β pathway, which are collectively regulated by the miR-15b-5p/TGFBR3 axis. Our present study provides a new perspective for necroptosis regulated by the miR-15b-5p/TGFBR3 axis and reveals a new form of inflammation regulation in immune diseases.
硫化氢（HS）是一种空气污染物，对免疫系统具有毒性作用。细胞程序性坏死（Necroptosis）已被讨论为一种新的细胞死亡形式，在炎症中发挥重要作用。为了研究 HS 诱导的免疫损伤机制，以及 microRNAs（miRNAs）在这一过程中的作用，我们基于高通量测序的结果，选择了变化最显著的 miR-15b-5p 进行后续实验。我们通过 miRDB、Targetscan 和双荧光素酶报告实验进一步预测和确定了 HD11 中 miR-15b-5p 和 TGFBR3 之间的靶向关系，并发现 miR-15b-5p 在 HS 诱导的程序性坏死和炎症中高度表达。为了了解 miR-15b-5p/TGFBR3 轴是否参与程序性坏死和炎症过程，我们进一步揭示了 miR-15b-5p 的高表达和 TGFBR3 的敲低可以诱导程序性坏死。 Nec-1 处理增强了细胞的存活率。值得注意的是，HS 暴露会引起氧化应激并激活 TGF-β 途径，这一过程受 miR-15b-5p/TGFBR3 轴的共同调节。本研究为 miR-15b-5p/TGFBR3 轴调控的程序性坏死提供了新视角，并揭示了免疫疾病中炎症调控的新形式。
