Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway

Acute lung injury (ALI) is a severe disease characterized by a pulmonary inflammatory response and oxidative stress. Triptolide has been demonstrated to have anti-inflammatory and antioxidant properties. Herein, we present triptolide-loaded mesenchymal stem cell–derived exosomes (MSC-Exos) as a mult...

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Main Authors: Ying Zhang, Fan Pan, Xiaotao Xu, Zhihua Jiao, Hong Xie, Aizhong Wang
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Canadian Respiratory Journal
Online Access:http://dx.doi.org/10.1155/2024/7240138
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author Ying Zhang
Fan Pan
Xiaotao Xu
Zhihua Jiao
Hong Xie
Aizhong Wang
author_facet Ying Zhang
Fan Pan
Xiaotao Xu
Zhihua Jiao
Hong Xie
Aizhong Wang
author_sort Ying Zhang
collection DOAJ
description Acute lung injury (ALI) is a severe disease characterized by a pulmonary inflammatory response and oxidative stress. Triptolide has been demonstrated to have anti-inflammatory and antioxidant properties. Herein, we present triptolide-loaded mesenchymal stem cell–derived exosomes (MSC-Exos) as a multifunctional biomimetic delivery system (Tri-Exos) for targeting injured lung tissue. The therapeutic effect of Tri-Exos on ALI was evaluated by measuring inflammatory cytokines content, the expression of myeloperoxidase (MPO), the number of immune cells in bronchoalveolar lavage fluid, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Subsequently, immunohistochemistry and Western blotting were used to assess the expression levels of critical proteins in the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway, autophagy pathway, apoptosis, and MAPK signaling pathway. The experimental results showed that LPS significantly increased pathological damage, secretion of inflammatory cytokines, and oxidative stress in lung tissue. However, treatment with Tri-Exos significantly alleviated this series of pathological changes. Tri-Exos significantly upregulated the expression of Nrf-2 signaling pathway–related proteins, autophagy, and apoptosis and inhibited the expression of MAPK signaling pathway-related proteins in the ALI model. Our study showed that Tri-Exos exerted a therapeutic effect on LPS-induced ALI by regulating the Nrf-2 signaling pathway–dependent autophagy and MAPK signaling pathway.
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spelling doaj-art-98fe6885c3e1445d88ffbe00d43fb9ea2025-08-20T03:37:23ZengWileyCanadian Respiratory Journal1916-72452024-01-01202410.1155/2024/7240138Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling PathwayYing Zhang0Fan Pan1Xiaotao Xu2Zhihua Jiao3Hong Xie4Aizhong Wang5Department of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyAcute lung injury (ALI) is a severe disease characterized by a pulmonary inflammatory response and oxidative stress. Triptolide has been demonstrated to have anti-inflammatory and antioxidant properties. Herein, we present triptolide-loaded mesenchymal stem cell–derived exosomes (MSC-Exos) as a multifunctional biomimetic delivery system (Tri-Exos) for targeting injured lung tissue. The therapeutic effect of Tri-Exos on ALI was evaluated by measuring inflammatory cytokines content, the expression of myeloperoxidase (MPO), the number of immune cells in bronchoalveolar lavage fluid, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Subsequently, immunohistochemistry and Western blotting were used to assess the expression levels of critical proteins in the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway, autophagy pathway, apoptosis, and MAPK signaling pathway. The experimental results showed that LPS significantly increased pathological damage, secretion of inflammatory cytokines, and oxidative stress in lung tissue. However, treatment with Tri-Exos significantly alleviated this series of pathological changes. Tri-Exos significantly upregulated the expression of Nrf-2 signaling pathway–related proteins, autophagy, and apoptosis and inhibited the expression of MAPK signaling pathway-related proteins in the ALI model. Our study showed that Tri-Exos exerted a therapeutic effect on LPS-induced ALI by regulating the Nrf-2 signaling pathway–dependent autophagy and MAPK signaling pathway.http://dx.doi.org/10.1155/2024/7240138
spellingShingle Ying Zhang
Fan Pan
Xiaotao Xu
Zhihua Jiao
Hong Xie
Aizhong Wang
Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
Canadian Respiratory Journal
title Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
title_full Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
title_fullStr Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
title_full_unstemmed Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
title_short Triptolide-Loaded Mesenchymal Stem Cell–Derived Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Induction of Nrf-2/HO-1 Signaling Pathway–Dependent Autophagy and Mitigation of MAPK Signaling Pathway
title_sort triptolide loaded mesenchymal stem cell derived exosomes ameliorates lipopolysaccharide induced acute lung injury via induction of nrf 2 ho 1 signaling pathway dependent autophagy and mitigation of mapk signaling pathway
url http://dx.doi.org/10.1155/2024/7240138
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