Notch 2 from bone marrow mesenchymal stem cells alleviates smoke inhalation-induced lung injury by mediating alveolar cell differentiation

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-03-22 DOI:10.1007/s10735-025-10393-8

Cunping Yin, Xiaoyan Wang, Yanmei Tao, Xiaoqing Wu, Yuan Li, Haiping Li, Yuan Liang

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引用次数: 0

Abstract

Background

Smoke inhalation-induced lung injury (SILI) is the major fatality in fire- and blast-related accidents. Bone marrow mesenchymal stem cells (BMSCs) have a potential therapeutic role in SILI through directional differentiation into AT1, AT2, and pulmonary vascular endothelial cells. The present study proposes to evaluate the effect of Notch 2 on the directional differentiation of BMSCs and to characterize its reparative role in a SILI model.

Methods

pGMLV-SC5 RNAi and pcDNA 3.1 lentivirus exogenously regulate Notch 2 expression in rat-derived BMSCs and BMSCs were injected into the tail vein of the SILI rat model. H&E, Masson and TUNEL stains characterized pathological changes in rat lung tissue. ELISA, western blot, and RT-qPCR identified inflammatory factors (IL-1β, IL-6 and TNF-α), Notch 2 pathway- (Notch 2 and Hes1), lung fibrosis- (α-SMA and E-cadherin), AT1- (AQP5), and AT2- (SPC and SPD) associated markers.

Results

pGMLV-SC5 RNAi or pcDNA 3.1 lentivirus could decrease or increase Notch 2 expression in BMSCs. In vivo imaging showed that BMSCs could be localized in the lungs of the SILI model at 24 h after model development. Treatment with BMSCs alleviated diffuse congestion, lung fibrosis, and alveolar cell apoptosis in lung tissues of the SILI model. Treatment of BMSCs decreased the levels of IL-1β, IL-6, TNF-α, and α-SMA and increased the expression of Notch 2, Hes1, E-cadherin, AQP5, SPC, and SPD in the SILI model. Overexpression of Notch 2 enhances the therapeutic effect of BMSCs on lung injury in the SILI model. Notably, overexpression of Notch 2 attenuated the BMSCs-induced upregulation of AQP5 expression and enhanced the BMSCs-induced upregulation of SPC and SPD expression.

Conclusion

Notch 2 contributes to lung injury repair in the SILI rat model by facilitating the differentiation of BMSCs to AT2. This study provides a new idea and target for the treatment of BMSCs for SILI.

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背景吸入烟雾引起的肺损伤（SILI）是火灾和爆炸相关事故中的主要致死原因。骨髓间充质干细胞（BMSCs）可定向分化为AT1、AT2和肺血管内皮细胞，从而在SILI中发挥潜在的治疗作用。方法spGMLV-SC5 RNAi 和 pcDNA 3.1 慢病毒外源调节大鼠来源的 BMSCs 中 Notch 2 的表达，并将 BMSCs 注入 SILI 大鼠模型的尾静脉。H&E、Masson和TUNEL染色显示了大鼠肺组织的病理变化。ELISA、Western blot和RT-qPCR鉴定了炎症因子（IL-1β、IL-6和TNF-α）、Notch 2通路（Notch 2和Hes1）、肺纤维化（α-SMA和E-cadherin）、AT1（AQP5）和AT2（SPC和SPD）相关标记物。体内成像显示，BMSCs 可在模型建立后 24 小时内在 SILI 模型的肺部定位。用 BMSCs 治疗可缓解 SILI 模型肺组织的弥漫性充血、肺纤维化和肺泡细胞凋亡。BMSCs 治疗降低了 SILI 模型中 IL-1β、IL-6、TNF-α 和 α-SMA 的水平，增加了 Notch 2、Hes1、E-cadherin、AQP5、SPC 和 SPD 的表达。在 SILI 模型中，Notch 2 的过表达增强了 BMSCs 对肺损伤的治疗效果。结论Notch 2通过促进BMSCs向AT2分化，有助于SILI大鼠模型的肺损伤修复。本研究为 BMSCs 治疗 SILI 提供了新的思路和靶点。

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

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.