Phenylacetylglutamine produced from injury lung alveolar epithelial cells promotes the function of BMSCs by regulating NONRATT006276.2/Mapt pathway.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2025-05-24 DOI:10.1186/s12931-025-03261-2

Tianyun Yang, Juan Peng, Rongrong Ren, Lin Song

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引用次数: 0

Abstract

Mesenchymal stem cell (MSC)-based therapy regenerates damaged structures of the respiratory system and restores lung function, thus providing a promising therapeutic approach for chronic obstructive pulmonary disease. Understanding the communication between injured alveolar cells and MSCs can improve the efficiency of MSC-based therapies. The present study analyzed the untargeted metabolomics of the supernatant of AEC-II injury induced by cigarette smoke extract and identified 205 differential metabolites. Phenotypic assays indicated that phenylacetylglutamine (PAG) significantly promoted the migration and mitochondrial function of bone marrow MSCs (BMSCs). Whole-transcriptome sequencing (WT-seq) was used to analyze the long noncoding RNA (lncRNA) and mRNA expression profiles of BMSCs treated with PAG. The upregulated lncNRA NONRATT006276.2 (NRT6276.2) and its trans-regulated gene, microtubule-associated protein tau (Mapt), were identified based on the lncRNA-mRNA co-expression network and bioinformatics analysis. The knockdown of NRT6276.2 or Mapt inhibited the positive effects of PAG on BMSCs. Furthermore, Mapt overexpression reversed the phenotype of BMSCs inhibited by silencing NRT6276.2. In conclusion, PAG enhanced the migration and mitochondrial function of BMSCs by regulating the NRT6276.2/Mapt pathway. This study clarified the positive effects of PAG produced by injured lung cells on transplanted MSCs, providing a potential new strategy to enhance the efficiency of MSC-based therapies.

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损伤肺泡上皮细胞产生的苯乙酰谷氨酰胺通过调节NONRATT006276.2/Mapt通路促进骨髓间充质干细胞的功能。

基于间充质干细胞（MSC）的治疗可再生呼吸系统受损结构并恢复肺功能，从而为慢性阻塞性肺疾病提供了一种有前景的治疗方法。了解损伤肺泡细胞与间充质干细胞之间的交流可以提高基于间充质干细胞的治疗效率。本研究分析了香烟烟雾提取物诱导AEC-II损伤上清的非靶向代谢组学，鉴定出205种差异代谢物。表型分析表明，苯乙酰谷氨酰胺（PAG）显著促进骨髓间充质干细胞（BMSCs）迁移和线粒体功能。采用全转录组测序（WT-seq）分析PAG处理的骨髓间充质干细胞的长链非编码RNA （lncRNA）和mRNA表达谱。基于lncRNA-mRNA共表达网络和生物信息学分析，鉴定了上调的lncrra NONRATT006276.2 （NRT6276.2）及其反式调控基因微管相关蛋白tau （Mapt）。NRT6276.2或Mapt基因的敲低抑制了PAG对骨髓间充质干细胞的积极作用。此外，Mapt过表达逆转了NRT6276.2沉默抑制的骨髓间充质干细胞的表型。综上所述，PAG通过调控NRT6276.2/Mapt通路增强骨髓间充质干细胞的迁移和线粒体功能。本研究阐明了损伤肺细胞产生的PAG对移植间充质干细胞的积极作用，为提高基于间充质干细胞的治疗效率提供了一种潜在的新策略。

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

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.