Silencing Map3k7 suppresses pyroptosis to alleviate bronchopulmonary dysplasia through inhibiting the TGF-β1/Smad3 pathway.

IF 1.3 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hong Zhen, Qiaozhen Wei, Bingmei Wei, Qingmei Huang, Ruishan Li
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引用次数: 0

Abstract

Bronchopulmonary dysplasia (BPD) is a serious complication in premature infants. This study aimed to investigate the mechanism of mitogen-activated protein 3 kinase 7 (Map3k7) affecting BPD by regulating caspase-1 mediated pyroptosis. The morphology of the lung tissue was observed using hematoxylin-eosin staining. TUNEL staining was performed to detect tissue apoptosis. RNA-seq and protein-protein interaction (PPI) network were performed to identify hub genes. Cell viability and apoptosis was analyzed using the CCK-8 assay and flow cytometry, respectively. Pyroptosis-related factors, inflammatory factors, oxidative stress indicators, and pathway-related proteins were detected using ELISA, qRT-PCR, and Western blotting. Hyperoxia-induced neonatal rats showed alveolar simplification with increased alveolar lumen, and decreased density of secondary alveolar cristae, demonstrating the successful BPD model. Map3k7 was identified as the crucial gene that was upregulated in BPD. Silencing Map3k7 promoted cell proliferation and suppressed apoptosis, inflammation, oxidative stress, and pyroptosis in hyperoxia-induced AEC-II, and alleviated BPD progression in hyperoxia-induced rats. Furthermore, silencing Map3k7 inhibited the TGF-β1/Smad3 pathway, and SRI-011381, the TGF-β pathway activator, weakened the inhibitory effects of silencing Map3k7 on hyperoxia-induced AEC-II. Silencing Map3k7 suppressed pyroptosis to alleviate BPD through inhibiting the TGF-β1/Smad3 pathway, providing a direction for the treatment of BPD in premature infants.

沉默Map3k7可通过抑制TGF-β1/Smad3通路抑制肺焦亡,缓解支气管肺发育不良。
支气管肺发育不良(BPD)是早产儿的严重并发症。本研究旨在探讨丝裂原活化蛋白3激酶7 (Map3k7)通过调节caspase-1介导的焦亡影响BPD的机制。苏木精-伊红染色观察肺组织形态。TUNEL染色检测组织凋亡。通过RNA-seq和蛋白相互作用(PPI)网络鉴定中心基因。分别采用CCK-8法和流式细胞术分析细胞活力和凋亡。采用ELISA、qRT-PCR、Western blotting检测热释热相关因子、炎症因子、氧化应激指标、途径相关蛋白。高氧诱导的新生大鼠肺泡简化,肺泡管腔增大,继发性肺泡嵴密度降低,表明BPD模型成功建立。Map3k7被确定为BPD中表达上调的关键基因。沉默Map3k7可促进高氧诱导的AEC-II细胞增殖,抑制细胞凋亡、炎症、氧化应激和焦亡,缓解高氧诱导大鼠BPD的进展。此外,沉默Map3k7可抑制TGF-β1/Smad3通路,而TGF-β通路激活剂SRI-011381可减弱沉默Map3k7对高氧诱导的AEC-II的抑制作用。沉默Map3k7通过抑制TGF-β1/Smad3通路抑制焦亡,缓解BPD,为早产儿BPD的治疗提供方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
General physiology and biophysics
General physiology and biophysics 生物-生化与分子生物学
CiteScore
2.70
自引率
0.00%
发文量
42
审稿时长
6-12 weeks
期刊介绍: General Physiology and Biophysics is devoted to the publication of original research papers concerned with general physiology, biophysics and biochemistry at the cellular and molecular level and is published quarterly by the Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences.
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