scholarly journals Secreted Phospholipase A2-IIA Modulates Transdifferentiation of Cardiac Fibroblast through EGFR Transactivation: An Inflammation–Fibrosis Link

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 396 ◽  
Author(s):  
Ruben Martin ◽  
Beatriz Gutierrez ◽  
Claudia Cordova ◽  
Alberto San Roman ◽  
Yolanda Alvarez ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Cardiac Fibroblast ◽  
Cardiac Remodelling ◽  
Myofibroblast Differentiation ◽  
Heparin Binding ◽  
Mice Model ◽  
Autoimmune Myocarditis ◽  
Egfr Transactivation ◽  
Secreted Phospholipase A2 ◽  
Ros Accumulation

Secreted phospholipase A2-IIA (sPLA2-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA2-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA2-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme lysyl oxidase (LOX) and reactive oxygen species (ROS) accumulation. Exogenous sPLA2-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA2-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1, LOX and collagen I. ROS accumulation were also found to be increased in sPLA2-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA2-IIA. In conclusion, sPLA2-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.

scholarly journals Role of human group IIA secreted phospholipase A2 in malaria pathophysiology: Insights from a transgenic mouse model

Biochimie ◽  
2021 ◽  
Author(s):  
Mélanie Dacheux ◽  
Soraya Chaouch ◽  
Alonso Joy ◽  
Amandine Labat ◽  
Christine Payré ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phospholipase A2 ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Human Group ◽  
Secreted Phospholipase A2

scholarly journals Group X Secreted Phospholipase A2 Limits the Development of Atherosclerosis in LDL Receptor–Null Mice

2013 ◽  
Vol 33 (3) ◽  
pp. 466-473 ◽  
Author(s):  
Hafid Ait-Oufella ◽  
Olivier Herbin ◽  
Charlotte Lahoute ◽  
Christelle Coatrieux ◽  
Xavier Loyer ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Ldl Receptor ◽  
Secreted Phospholipase A2

scholarly journals Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation

Blood ◽  
2014 ◽  
Vol 124 (14) ◽  
pp. 2173-2183 ◽  
Author(s):  
Luc H. Boudreau ◽  
Anne-Claire Duchez ◽  
Nathalie Cloutier ◽  
Denis Soulet ◽  
Nicolas Martin ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Rickettsia Prowazekii ◽  
Platelet Storage ◽  
Secreted Phospholipase A2 ◽  
Molecular Pattern ◽  
Key Points

Key Points When activated and in platelet storage bags, platelets release respiratory-competent mitochondria, a recognized damage-associated molecular pattern. Mitochondria, descendant of Rickettsia prowazekii, serve as substrate for bactericidal sPLA2-IIA to promote inflammation.

scholarly journals Relationship between levels of secreted phospholipase A2 groups IIA and X in the airways and asthma severity

2011 ◽  
Vol 41 (6) ◽  
pp. 801-810 ◽  
Author(s):  
T. S. Hallstrand ◽  
Y. Lai ◽  
Z. Ni ◽  
R. C. Oslund ◽  
W. R. Henderson ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Asthma Severity ◽  
Secreted Phospholipase A2

scholarly journals Critical Role of TLR2 and MyD88 for Functional Response of Macrophages to a Group IIA-Secreted Phospholipase A2 from Snake Venom

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93741 ◽  
Author(s):  
Elbio Leiguez ◽  
Karina Cristina Giannotti ◽  
Vanessa Moreira ◽  
Márcio Hideki Matsubara ◽  
José María Gutiérrez ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Functional Response ◽  
Snake Venom ◽  
Critical Role ◽  
Secreted Phospholipase A2

Renaturation and one step purification of the chicken GIIA secreted phospholipase A2 from inclusion bodies

2014 ◽  
Vol 67 ◽  
pp. 85-90 ◽  
Author(s):  
Aida Karray ◽  
Sawsan Amara ◽  
Frédéric Carrière ◽  
Youssef Gargouri ◽  
Sofiane Bezzine
Keyword(s):  
Phospholipase A2 ◽  
Inclusion Bodies ◽  
Secreted Phospholipase A2 ◽  
One Step

scholarly journals Trypanosoma cruzi Induces the PARP1/AP-1 Pathway for Upregulation of Metalloproteinases and Transforming Growth Factor β in Macrophages: Role in Cardiac Fibroblast Differentiation and Fibrosis in Chagas Disease

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Subhadip Choudhuri ◽  
Nisha Jain Garg
Keyword(s):  
Growth Factor ◽  
Chagas Disease ◽  
Transcriptional Activation ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cardiac Fibroblast ◽  
Myofibroblast Differentiation ◽  
Content Type ◽  
Parp1 Inhibitors

ABSTRACT Chagas disease (CD), caused by Trypanosoma cruzi, is a degenerative heart condition. In the present study, we investigated the role of poly [ADP-ribose] polymerase 1/activator protein 1 (PARP1/AP-1) in upregulation of profibrotic macrophages (Mϕ) and subsequent development of cardiac fibrosis in CD. We used in vitro and in vivo models of T. cruzi infection and chemical and genetic inhibition of Parp1 to examine the molecular mechanisms by which Mϕ might augment profibrotic events in CD. Cultured (RAW 264.7 and THP-1) Mϕ infected with T. cruzi and primary cardiac and splenic Mϕ of chronically infected mice exhibited a significant increase in the expression, activity, and release of metalloproteinases (MMP2, MMP9, and MMP12) and the cytokine transforming growth factor β (TGF-β). Mϕ release of MMPs and TGF-β signaled the cardiac fibroblast to myofibroblast differentiation, as evidenced by a shift from S100A4 to alpha smooth muscle actin (α-SMA) expression. Incubation of infected Mϕ with MMP2 and MMP9 inhibitors resulted in 60 to 74% decline in TGF-β release, and MMP9 and PARP1 inhibitors resulted in 57 to 70% decline in Mϕ TGF-β-driven cardiac fibroblast differentiation. Likewise, histological studies showed a 12- to 16-fold increase in myocardial expression of CD68 (Mϕ marker) and its colocalization with MMP9/TGF-β, galectin-3, and vimentin in wild-type mice with CD. In comparison, chronically infected Parp1−/− mice exhibited a >50% decline in myocardial levels of Mϕ and associated fibrosis markers. Further study showed that PARP1 synergized with c-Fos and JunB AP-1 family members for transcriptional activation of profibrotic response after T. cruzi infection. We conclude that PARP1 inhibition offers a potential therapy for controlling the T. cruzi-driven fibroblast differentiation in CD through modulation of the Mϕ signaling of the AP-1–MMP9–TGF-β pathway. IMPORTANCE Cardiomyopathy is the most important clinical manifestation of T. cruzi-driven CD. Recent studies have suggested the detrimental role of the matrix metalloproteinases MMP2 and MMP9 in extracellular matrix (ECM) degradation during cardiac remodeling in T. cruzi infection. Peripheral TGF-β levels are increased in clinically symptomatic CD patients over those in clinically asymptomatic seropositive individuals. We provide the first evidence that during T. cruzi infection, Mϕ release of MMP2 and MMP9 plays an active role in activation of TGF-β signaling of ECM remodeling and cardiac fibroblast-to-myofibroblast differentiation. We also determined that PARP1 signals c-Fos- and JunB-mediated AP-1 transcriptional activation of profibrotic gene expression and demonstrated the significance of PARP1 inhibition in controlling chronic fibrosis in Chagas disease. Our study provides a promising therapeutic approach for controlling T. cruzi-driven fibroblast differentiation in CD by PARP1 inhibitors through modulation of the Mϕ signaling of the AP-1–MMP9–TGF-β pathway.

Control of Eicosanoid Production by Cellular and Secreted Phospholipase A2

2004 ◽  
pp. 17-27
Author(s):  
Marise Andreani ◽  
Jean-Luc Olivier ◽  
Gilbert Béréziat
Keyword(s):  
Phospholipase A2 ◽  
Eicosanoid Production ◽  
Secreted Phospholipase A2

Plasma secreted phospholipase A2 in asthmatic children: correlation with leptin levels and exercise induced bronchoconstriction

2015 ◽  
Vol 3 (2) ◽  
pp. 99
Author(s):  
Jueng-Sup You ◽  
Won-Bok Choi ◽  
Yoon-Young Yi ◽  
Soo-In Jeong ◽  
Joon-Sup Song ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Asthmatic Children ◽  
Secreted Phospholipase A2 ◽  
Exercise Induced

scholarly journals Group V Secreted Phospholipase A2 Is Upregulated by IL-4 in Human Macrophages and Mediates Phagocytosis via Hydrolysis of Ethanolamine Phospholipids

2015 ◽  
Vol 194 (7) ◽  
pp. 3327-3339 ◽  
Author(s):  
Julio M. Rubio ◽  
Juan P. Rodríguez ◽  
Luis Gil-de-Gómez ◽  
Carlos Guijas ◽  
María A. Balboa ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Group V ◽  
Human Macrophages ◽  
Secreted Phospholipase A2 ◽  
Hydrolysis Of
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