Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombos...

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Main Authors: Qiang Li, Xiaoxiao Fu, Jiang Yuan, Shu Han
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/8876484
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author Qiang Li
Xiaoxiao Fu
Jiang Yuan
Shu Han
author_facet Qiang Li
Xiaoxiao Fu
Jiang Yuan
Shu Han
author_sort Qiang Li
collection DOAJ
description Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of “anti-inflammatory” T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.
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spelling doaj-art-071a0be4fcc8456cbc16666fa3bc11662025-08-20T03:55:24ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/88764848876484Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress SyndromeQiang Li0Xiaoxiao Fu1Jiang Yuan2Shu Han3The Emergency Department, The Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU), Hangzhou, ChinaInstitute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, ChinaDepartment of Pulmonology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, ChinaInstitute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, ChinaThrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of “anti-inflammatory” T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.http://dx.doi.org/10.1155/2021/8876484
spellingShingle Qiang Li
Xiaoxiao Fu
Jiang Yuan
Shu Han
Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
Mediators of Inflammation
title Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
title_full Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
title_fullStr Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
title_full_unstemmed Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
title_short Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome
title_sort contribution of thrombospondin 1 and 2 to lipopolysaccharide induced acute respiratory distress syndrome
url http://dx.doi.org/10.1155/2021/8876484
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