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Prostaglandins and actin remodelling

Inés C Osma-Garcia, Carmen Punzón, Manuel Fresno, Manuel D Díaz-Muñoz
Macrophage migration to the focus of infection is a hallmark of the innate immune response. Macrophage spreading, adhesion, and migration through the extracellular matrix require dynamic remodeling of the actin cytoskeleton associated to integrin clustering in podosomes and focal adhesions. Here, we show that prostaglandin E2 (PGE2 ), the main prostaglandin produced by macrophages during inflammation, promote the distinctive dose-dependent formation of podosomes or focal adhesions in macrophages. Low concentrations of PGE2 increased p110γ PI3K expression, phosphorylation of actin-related protein 2, and formation of podosomes, which enhanced macrophage migration in response to chemokines...
March 2016: European Journal of Immunology
Hayley C Warsinske, Shanna L Ashley, Jennifer J Linderman, Bethany B Moore, Denise E Kirschner
Fibroblasts play an important role in the wound-healing process by generating extracellular matrix (ECM) and undergoing differentiation into myofibroblasts, but these cells can also be involved in pathologic remodeling of tissue. Nascent ECM provides a substrate for re-epithelialization to occur, restoring damaged tissue to a functional state. Dysregulation of this process can result in fibrosis--stiffening and scarring of the tissue. Current treatments cannot halt or reverse this process. The molecular mechanisms underlying fibrotic dysregulation are poorly understood, providing an untapped pool of potential therapeutic targets...
August 2015: Bulletin of Mathematical Biology
Ewa Kautz, Paula de Carvalho Papa, Iris M Reichler, Aykut Gram, Alois Boos, Mariusz P Kowalewski
BACKGROUND: The uterine response to the presence of embryos is poorly understood in the domestic dog (Canis familiaris). The intimate embryo-maternal cross-talk, which begins following the hatching of blastocysts and embryo attachment leads to strong structural and functional remodelling of the uterus. A part of this process is decidualisation, comprising morphological and biochemical changes that result in formation of maternal stroma-derived decidual cells. These are an integral part of the canine placenta materna, which together with the maternal vascular endothelium are the only cells of the canine endotheliochorial placenta able to resist trophoblast invasion...
2015: Reproductive Biology and Endocrinology: RB&E
Nithiananthan Asokananthan, Rommel S Lan, Peter T Graham, Anthony J Bakker, Ana Tokanović, Geoffrey A Stewart
Previous studies have shown that protease-activated receptors (PARs) play an important role in various physiological processes. In the present investigation, we determined the expression of PARs on human lung fibroblasts (HLF-1) and whether they were involved in cellular differentiation and pro-inflammatory cytokine and prostaglandin (PGE2) secretion. PAR-1, PAR-2, PAR-3, and PAR-4 were detected in fibroblasts using RT-PCR, immunocytochemistry, and flow cytometry. Increased expression of PAR-4, but not other PARs, was observed in fibroblasts stimulated with phorbol myristate acetate...
February 1, 2015: Physiological Reports
A Romero, M Cáceres, R Arancibia, D Silva, E Couve, C Martínez, J Martínez, P C Smith
BACKGROUND: Granulation tissue remodeling and myofibroblastic differentiation are critically important events during wound healing. Tobacco smoking has a detrimental effect in gingival tissue repair. However, studies evaluating the effects of cigarette smoke on these events are lacking. MATERIAL AND METHODS: We used gingival fibroblasts cultured within free-floating and restrained collagen gels to simulate the initial and final steps of the granulation tissue phase during tissue repair...
June 2015: Journal of Periodontal Research
Xiaoyuan Gong, Weidong Yang, Liyun Wang, Randall L Duncan, Jun Pan
The effect of prostaglandin E2 (PGE2) on bone mass has been well-established in vivo. Previous studies have showed that PGE2 increases differentiation, proliferation, and regulates cell morphology through F-actin stress fiber in statically cultured osteoblasts. However, the effect of PGE2 on osteoblasts in the presence of fluid shear stress (FSS), which could better uncover the anabolic effect of PGE2 in vivo, has yet to be examined. Here, we hypothesized that PGE2 modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 osteoblastic cells through protein kinase A (PKA) pathway...
January 2014: Acta Biochimica et Biophysica Sinica
Andrew J Spracklen, Daniel J Kelpsch, Xiang Chen, Cassandra N Spracklen, Tina L Tootle
Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX) enzymes--regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin remodeling, including actin filaments and aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles exhibit similar structures at a low frequency...
February 2014: Molecular Biology of the Cell
William T Gerthoffer, Julian Solway, Blanca Camoretti-Mercado
Significant advances in understanding the cell and molecular biology of inflammation and airway smooth muscle (ASM) contractility have identified several potential novel targets for therapies of asthma. New agents targeting G-protein coupled receptors (GPCRs) including bitter taste receptors (TAS2R) agonists and prostaglandin EP4 receptor agonists elicit ASM relaxation. The cAMP/PKA pathway continues to be a promising drug target with the emergence of new PDE inhibitors and a novel PKA target protein, HSP20, which mediates smooth muscle relaxation via actin depolymerization...
June 2013: Current Opinion in Pharmacology
Christopher M Groen, Andrew J Spracklen, Tiffany N Fagan, Tina L Tootle
Although prostaglandins (PGs)-lipid signals produced downstream of cyclooxygenase (COX) enzymes-regulate actin cytoskeletal dynamics, their mechanisms of action are unknown. We previously established Drosophila oogenesis, in particular nurse cell dumping, as a new model to determine how PGs regulate actin remodeling. PGs, and thus the Drosophila COX-like enzyme Pxt, are required for both the parallel actin filament bundle formation and the cortical actin strengthening required for dumping. Here we provide the first link between Fascin (Drosophila Singed, Sn), an actin-bundling protein, and PGs...
December 2012: Molecular Biology of the Cell
A S Tarnawski, A Ahluwalia
In this paper we reviewed and updated current views on the cellular and molecular mechanisms of gastric and esophageal ulcer healing. Gastric ulcer healing encompasses inflammation, cell proliferation, epithelial regeneration, gland reconstruction, formation of granulation tissue, neovascularization (new blood vessel formation), interactions between various cells and the matrix and tissue remodeling, resulting in scar formation. All these events are controlled by the cytokines and growth factors, GI hormones including gastrin, CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins...
2012: Current Medicinal Chemistry
Elena A Goncharova, Dmitry A Goncharov, Hengjiang Zhao, Raymond B Penn, Vera P Krymskaya, Reynold A Panettieri
Severe asthma manifests as airway remodeling and irreversible airway obstruction, in part because of the proliferation and migration of human airway smooth muscle (HASM) cells. We previously reported that cyclic adenosine monophosphate-mobilizing agents, including β(2)-adrenergic receptor (β(2)AR) agonists, which are mainstay of asthma therapy, and prostaglandin E2 (PGE2), inhibit the migration of HASM cells, although the mechanism for this migration remains unknown. Vasodilator-stimulated phosphoprotein (VASP), an anticapping protein, modulates the formation of actin stress fibers during cell motility, and is negatively regulated by protein kinase A (PKA)-specific inhibitory phosphorylation at serine 157 (Ser157)...
January 2012: American Journal of Respiratory Cell and Molecular Biology
Suman Dwivedi, Dharmendra Pandey, Anna L Khandoga, Richard Brandl, Wolfgang Siess
BACKGROUND: Platelet activation requires rapid remodeling of the actin cytoskeleton which is regulated by small GTP-binding proteins. By using the Rac1-specific inhibitor NSC23766, we have recently found that Rac1 is a central component of a signaling pathway that regulates dephosphorylation and activation of the actin-dynamising protein cofilin, dense and α-granule secretion, and subsequent aggregation of thrombin-stimulated washed platelets. OBJECTIVES: To study whether NSC23766 inhibits stimulus-induced platelet secretion and aggregation in blood...
December 6, 2010: Journal of Translational Medicine
Eugénie Goupil, Danaë Tassy, Carine Bourguet, Christiane Quiniou, Veronica Wisehart, Darlaine Pétrin, Christian Le Gouill, Dominic Devost, Hans H Zingg, Michel Bouvier, Horacio Uri Saragovi, Sylvain Chemtob, William D Lubell, Audrey Claing, Terence E Hébert, Stéphane A Laporte
The prostaglandin F2alpha (PGF2alpha) receptor (FP) is a key regulator of parturition and a target for pharmacological management of preterm labor. However, an incomplete understanding of signaling pathways regulating myometrial contraction hinders the development of improved therapeutics. Here we used a peptidomimetic inhibitor of parturition in mice, PDC113.824, whose structure was based on the NH(2)-terminal region of the second extracellular loop of FP receptor, to gain mechanistic insight underlying FP receptor-mediated cell responses in the context of parturition...
August 13, 2010: Journal of Biological Chemistry
Anthony J Hutchinson, Serena C Coons, Chih-Ling Chou, Wei Xu, W Daniel Stamer, David F Woodward, John W Regan
PURPOSE: Agonists of the F prostanoid receptor for prostaglandin F2alpha exert. exert an ocular hypotensive effect that has been attributed to increased aqueous humor outflow through the uveoscleral pathway. Although tissue remodeling of the ciliary muscle has been described, the signaling mechanisms that link activation of the FP receptor to remodeling of the ciliary muscle are poorly understood. Herein, we describe the identification of novel signaling mechanisms that may contribute to this process...
May 2010: Current Eye Research
C Schell, M Albrecht, S Spillner, C Mayer, L Kunz, F M Köhn, U Schwarzer, A Mayerhofer
The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility...
March 2010: Endocrinology
K J Sales, S C Boddy, H N Jabbour
Cellular adhesion to extracellular matrix is a central phenomenon for the maintenance of tissue integrity and cellular movement. Collectively, these processes are regulated by a fine-tuned balance between the formation and loosening of adhesive contacts, a process involving integrins, and the elevation and diminution of cytoplasmic signalling molecules. We demonstrate that prostaglandin (PG) F(2alpha) stimulation rapidly increases the capacity of Ishikawa cells stably expressing the F-prostanoid receptor (FPS) to adhere to vitronectin...
April 10, 2008: Oncogene
Anna A Birukova, Tatiana Zagranichnaya, Panfeng Fu, Elena Alekseeva, Weiguo Chen, Jeffrey R Jacobson, Konstantin G Birukov
Prostaglandin E(2) (PGE(2)) and prostacyclin are lipid mediators produced by cyclooxygenase and implicated in the regulation of vascular function, wound repair, inflammatory processes, and acute lung injury. Although protective effects of these prostaglandins (PGs) are associated with stimulation of intracellular cAMP production, the crosstalk between cAMP-activated signal pathways in the regulation of endothelial cell (EC) permeability is not well understood. We studied involvement of cAMP-dependent kinase (PKA), cAMP-Epac-Rap1 pathway, and small GTPase Rac in the PGs-induced EC barrier protective effects and cytoskeletal remodeling...
July 1, 2007: Experimental Cell Research
Yoshihiro Fukumoto, Shunsuke Tawara, Hiroaki Shimokawa
Pulmonary arterial hypertension (PAH) is a disease with poor prognosis characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary artery hyperconstriction and remodeling. However, the precise mechanism of PAH still remains to be elucidated. Although anticoagulant agents, vasodilators (e.g., prostaglandins, sildenafil, and bosentan), and lung transplantation are currently used for the treatment of PAH, more effective treatment needs to be developed. Rho-kinase causes vascular smooth muscle hyperconstriction and vascular remodeling through inhibition of myosin phosphatase and activation of its downstream effectors...
April 2007: Tohoku Journal of Experimental Medicine
Geneviève Laroche, Moulay Driss Rochdi, Stéphane A Laporte, Jean-Luc Parent
The role of actin in endocytosis of G protein-coupled receptors is poorly defined. In the present study, we demonstrate that agents that depolymerize (latrunculin B and cytochalasin D) or stabilize (jasplakinolide) the actin cytoskeleton blocked agonist-induced endocytosis of the beta isoform of the thromboxane A(2) receptor (TPbeta) in HEK293 cells. This suggests that endocytosis of TPbeta requires active remodeling of the actin cytoskeleton. On the other hand, disruption of microtubules with colchicine did not affect endocytosis of the receptor...
June 17, 2005: Journal of Biological Chemistry
Sandrine De Seranno, Cecilia Estrella, Anne Loyens, Anda Cornea, Sergio R Ojeda, Jean-Claude Beauvillain, Vincent Prevot
Glial and endothelial cells interact throughout the brain to define specific functional domains. Whether endothelial cells convey signals to glia in the mature brain is unknown but is amenable to examination in circumventricular organs. Here we report that purified endothelial cells of one of these organs, the median eminence of the hypothalamus, induce acute actin cytoskeleton remodeling in isolated ependymoglial cells and show that this plasticity is mediated by nitric oxide (NO), a diffusible factor. We found that both soluble guanylyl cyclase and cyclooxygenase products are involved in this endothelial-mediated control of ependymoglia cytoarchitecture...
November 17, 2004: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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