← Back to Search
Exosome-delivered Syndecan-1 Rescues Acute Lung Injury Via FAK/p190RhoGAP/RhoA/ROCK/NF-κB Signaling Axis And Glycocalyx Enhancement.
C. Zhang, F. Guo, Mengling Chang, Zengding Zhou, L. Yi, Chengjin Gao, Xiaoqin Huang, J. Huan
Published 2019 · Biology, Medicine
Download PDFAnalyze on Scholarcy
Acute lung injury (ALI) is characterized by protein-rich pulmonary edema, critical hypoxemia, and influx of pro-inflammatory cytokines and cells. There are currently no effective pharmacon therapies in clinical practice. Syndecan-1 in endothelial cells has potential to protect barrier function of endothelium and suppress inflammation response. Thus, the present study was to identify whether exosomes with encapsulation of syndecan-1 could achieve ideal therapeutic effects in ALI. Exosomes were isolated from the conditional medium of lentivirus-transfected mouse pulmonary microvascular endothelial cells (MPMVECs) and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blotting. ALI mouse models were induced via intratracheal administration of lipopolysaccharide (LPS) and treated with exosomes. Lung edema, inflammation, and glycocalyx thickness were examined. The possible mechanism was verified by immunoblotting in MPMVECs. The purified exosomes included SDC1-high-Exos and SDC1-low-Exos which loaded with up-regulated syndecan-1 and down-regulated syndecan-1 respectively. Compared with SDC1-low-Exos, administration of SDC1-high-Exos could ameliorate lung edema and inflammation, attenuate number of cells and protein levels in bronchoalveolar lavage fluid (BALF), and preserve glycocalyx. Furthermore, SDC1-high-Exos also mitigated the expression of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 following LPS challenge. In MPMVECs, SDC1-high-Exos decreased stress fiber formation and ameliorated monolayer hyper-permeability after LPS stimulation. Western blotting analysis demonstrated that FAK/p190RhoGAP/RhoA/ROCK/NF-κB signaling pathway may be involved in LPS-induced ALI. In conclusion, SDC1-high-Exos play a pivotal role in ameliorating LPS-stimulated ALI models and may be served as a potential therapeutic agent for clinical application in the future.
This paper references
Syndecan-1 enhances the endometrial cancer invasion by modulating matrix metalloproteinase-9 expression through nuclear factor kappaB.
J. Oh (2009)
Risk factors for the development of acute lung injury in patients with septic shock: An observational cohort study*
Remzi Iscimen (2008)
The epidemiology of sepsis in the United States from 1979 through 2000.
G. Martin (2003)
Apelin-13 Administration Protects Against LPS-Induced Acute Lung Injury by Inhibiting NF-κB Pathway and NLRP3 Inflammasome Activation
H. Zhang (2018)
Liposomal delivery of proteins and peptides
Janani Swaminathan (2012)
The endothelium in acute lung injury/acute respiratory distress syndrome
N. Maniatis (2008)
Molecular functions of syndecan-1 in disease.
Yvonne Hui-Fang Teng (2012)
Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix.
Jochen Steppan (2011)
The endothelial glycocalyx: a potential barrier between health and vascular disease
M. Nieuwdorp (2005)
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Lydia Alvarez-Erviti (2011)
Permeation of the luminal capillary glycocalyx is determined by hyaluronan.
C. B. Henry (1999)
An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals.
G. Matute-Bello (2011)
Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007
T. Lagu (2012)
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.
A. Montecalvo (2012)
Dual roles of heparanase in human carotid plaque calcification.
S. Aldi (2019)
Targeting of syndecan‐1 by microRNA miR‐10b promotes breast cancer cell motility and invasiveness via a Rho‐GTPase‐ and E‐cadherin‐dependent mechanism
S. Ibrahim (2012)
Lipoproteins in inflammation and sepsis. II. Clinical aspects
M. Wendel (2006)
GEF-H1-RhoA signaling pathway mediates LPS-induced NF-κB transactivation and IL-8 synthesis in endothelial cells.
F. Guo (2012)
LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK
H. Eutamene (2005)
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells.
Shin-ichiro Ohno (2013)
Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis.
R. Brauer (2016)
Exosomes: extracellular organelles important in intercellular communication.
S. Mathivanan (2010)
Fresh Frozen Plasma Lessens Pulmonary Endothelial Inflammation and Hyperpermeability After Hemorrhagic Shock and Is Associated With Loss of Syndecan 1
Zhanglong Peng (2013)
Tumor Necrosis Factor &agr; Decreases Nitric Oxide Synthase Type 3 Expression Primarily via Rho/Rho Kinase in the Thick Ascending Limb
Vanesa D. Ramseyer (2012)
The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome.
W. Aird (2003)
Amifostine reduces lung vascular permeability via suppression of inflammatory signalling
P. Fu (2009)
Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP
Michael Holinstat (2006)
The acute respiratory distress syndrome.
M. Matthay (2012)
Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity
J. Li (2013)
Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles.
Ahmed A. Eltoukhy (2014)
Suppression of inflammation and acute lung injury by the transcription factor Miz1 via repression of C/EBP-δ
Hanh Chi Do-Umehara (2013)
Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation.
M. Nieuwdorp (2009)
LPS-induced MCP-1 expression in human microvascular endothelial cells is mediated by the tyrosine kinase, Pyk2 via the p38 MAPK/NF-kappaB-dependent pathway.
A. Anand (2009)
Exosomes: composition, biogenesis and function
C. Théry (2002)
Capillary endothelial surface layer selectively reduces plasma solute distribution volume.
H. Vink (2000)
Attenuation of endotoxin-induced acute lung injury by the Rho-associated kinase inhibitor, Y-27632.
S. Tasaka (2005)
Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma
F. Felicetti (2016)
Clinical risks for development of the acute respiratory distress syndrome.
L. Hudson (1995)
The Rho-kinase inhibitor fasudil restores normal motor nerve conduction velocity in diabetic rats by assuring the proper localization of adhesion-related molecules in myelinating Schwann cells
Yasushi Kanazawa (2013)
INCREASED EXPRESSION OF SYNDECAN-1 PROTECTS AGAINST CARDIAC DILATATION AND DYSFUNCTION AFTER MYOCARDIAL INFARCTION.: PH.5
D. Vanhoutte (2007)
Application of albumin prior to delayed thrombolysis reduces brain edema and blood brain barrier permeability in an embolic stroke model
H. Lu (2012)
Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions
H. Okada (2017)
Phosphorylation of Myosin-Binding Subunit (Mbs) of Myosin Phosphatase by Rho-Kinase in Vivo
Yoji Kawano (1999)
Signaling mechanisms regulating endothelial permeability.
D. Mehta (2006)
Syndecan-1 Acts in Synergy with Tight Junction Through Stat3 Signaling to Maintain Intestinal Mucosal Barrier and Prevent Bacterial Translocation
Zhongqiu Wang (2015)
Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations.
M. Kim (2018)
The immunopathogenesis of sepsis
J. Cohen (2002)
Syndecan-1 Is an in Vivo Suppressor of Gram-positive Toxic Shock*
K. Hayashida (2008)
Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia
Risa Inagawa (2018)
Microglia-derived HIV Nef+ exosome impairment of the blood–brain barrier is treatable by nanomedicine-based delivery of Nef peptides
A. Raymond (2015)
Cell surface‐anchored syndecan‐1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis
Y. Zhang (2017)
GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury
L. Yi (2017)
Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury.
Jiping Zhao (2016)
Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome
Y. Zhang (2016)
Developmental differences in focal adhesion kinase expression modulate pulmonary endothelial barrier function in response to inflammation.
L. Ying (2018)
Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice
R. F. Righetti (2018)
Heparanase Regulates Secretion, Composition, and Function of Tumor Cell-derived Exosomes*♦
Camilla A Thompson (2013)
Cyclic AMP Blocks Bacterial Lipopolysaccharide-Induced Myosin Light Chain Phosphorylation in Endothelial Cells Through Inhibition of Rho/Rho Kinase Signaling1
M. Essler (2000)
Amelioration of sepsis by TIE2 activation–induced vascular protection
S. Han (2016)
Loss of Syndecan-1 Induces a Pro-inflammatory Phenotype in Endothelial Cells with a Dysregulated Response to Atheroprotective Flow*
Peter L. Voyvodic (2014)
The pathophysiology and treatment of sepsis.
R. Hotchkiss (2003)
Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature.
M. Götte (2002)
The Tyrosine Kinase Pyk2 Mediates Lipopolysaccharide-Induced IL-8 Expression in Human Endothelial Cells1
A. Anand (2008)
Experimental Study of the Protective Effect of Simvastatin on Lung Injury in Rats with Sepsis
Yu Wang (2017)
The Endothelial Glycocalyx Protects Against Myocardial Edema
B. M. van den Berg (2003)
Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway
Shuang Shi (2017)
Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding
N. Cui (2015)
A cytoplasmic C-terminal fragment of syndecan-1 is generated by sequential proteolysis and antagonizes syndecan-1 dependent lung tumor cell migration
T. Pasqualon (2015)
Hypothalamic stem cells control aging speed partly through exosomal miRNAs
Y. Zhang (2017)
This paper is referenced by
Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity
Thibault Annaval (2020)
Therapeutic effects of mangiferin on sepsis-associated acute lung and kidney injuries via the downregulation of vascular permeability and protection of inflammatory and oxidative damages.
D. Zhang (2020)
Syndecans in Inflammation at a Glance
Sandeep Gopal (2020)
Injured tubular epithelial cells activate fibroblasts to promote kidney fibrosis through miR-150-containing exosomes.
H. Guan (2020)
F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through MKL1 and YAP/TAZ
Zhicheng Tong (2020)
Systematic review of extracellular vesicle-based treatments for lung injury: are EVs a potential therapy for COVID-19?
K. Khalaj (2020)
Endothelial Progenitor Cell-Derived Extracellular Vesicles: A Novel Candidate for Regenerative Medicine and Disease Treatment.
Z. Xing (2020)
Exosome engineering: Current progress in cargo loading and targeted delivery
Shengyang Fu (2020)
Targeting Endothelial Dysfunction in Acute Critical Illness to Reduce Organ Failure
N. Juffermans (2020)