scholarly journals Cell type-specific roles of PAR1 in Coxsackievirus B3 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael F. Bode ◽  
Clare M. Schmedes ◽  
Grant J. Egnatz ◽  
Vanthana Bharathi ◽  
Yohei M. Hisada ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Fibroblasts ◽  
Coxsackievirus B3 ◽  
Poly I:C ◽  
Cell Type ◽  
Embryonic Fibroblasts ◽  
Cell Type Specific ◽  
Protease Activated Receptor 1 ◽  
Inflammatory Infiltrates ◽  
Specific Deletion

AbstractProtease-activated receptor 1 (PAR1) is widely expressed in humans and mice, and is activated by a variety of proteases, including thrombin. Recently, we showed that PAR1 contributes to the innate immune response to viral infection. Mice with a global deficiency of PAR1 expressed lower levels of CXCL10 and had increased Coxsackievirus B3 (CVB3)-induced myocarditis compared with control mice. In this study, we determined the effect of cell type-specific deletion of PAR1 in cardiac myocytes (CMs) and cardiac fibroblasts (CFs) on CVB3-induced myocarditis. Mice lacking PAR1 in either CMs or CFs exhibited increased CVB3 genomes, inflammatory infiltrates, macrophages and inflammatory mediators in the heart and increased CVB3-induced myocarditis compared with wild-type controls. Interestingly, PAR1 enhanced poly I:C induction of CXCL10 in rat CFs but not in rat neonatal CMs. Importantly, activation of PAR1 reduced CVB3 replication in murine embryonic fibroblasts and murine embryonic cardiac myocytes. In addition, we showed that PAR1 reduced autophagy in murine embryonic fibroblasts and rat H9c2 cells, which may explain how PAR1 reduces CVB3 replication. These data suggest that PAR1 on CFs protects against CVB3-induced myocarditis by enhancing the anti-viral response whereas PAR1 on both CMs and fibroblasts inhibits viral replication.

scholarly journals Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses

2007 ◽  
Vol 81 (24) ◽  
pp. 13668-13680 ◽  
Author(s):  
Jennifer Zurney ◽  
Kristina E. Howard ◽  
Barbara Sherry
Keyword(s):  
Cardiac Myocytes ◽  
Cardiac Fibroblasts ◽  
Viral Myocarditis ◽  
Cell Types ◽  
Cell Type ◽  
Organ Protection ◽  
Integrated Network ◽  
Basal Expression ◽  
Cell Type Specific ◽  
Β Receptor

ABSTRACT Viral myocarditis is an important human disease, and reovirus-induced murine myocarditis provides an excellent model system for study. Cardiac myocytes, like neurons in the central nervous system, are not replenished, yet there is no cardiac protective equivalent to the blood-brain barrier. Thus, cardiac myocytes may have evolved a unique antiviral response relative to readily replenished cell types, such as cardiac fibroblasts. Our previous comparisons of these two cell types revealed a conundrum: reovirus T3D induces more beta-interferon (IFN-β) mRNA in cardiac myocytes, yet there is a greater induction of IFN-stimulated genes (ISGs) in cardiac fibroblasts. Here, we investigated possible underlying molecular determinants. We found that greater basal expression of IFN-β in cardiac myocytes results in greater basal activated nuclear STAT1 and STAT2 and greater basal ISG mRNA expression and provides greater basal antiviral protection relative to cardiac fibroblasts. Conversely, cardiac fibroblasts express greater basal IFN-α/β receptor 1 (IFNAR1) and greater basal cytoplasmic Jak1, Tyk2, STAT2, and IRF9, leading to a greater increase in reovirus T3D- or IFN-induced nuclear activated STAT1 and STAT2 and greater induction of ISGs for a greater IFN-induced antiviral protection relative to cardiac myocytes. Our results suggest that high basal IFN-β expression in cardiac myocytes prearms this vulnerable, nonreplenishable cell type, while high basal expression of IFNAR1 and latent Jak-STAT components in adjacent cardiac fibroblasts renders these cells more responsive to IFN and prevents them from inadvertently serving as a reservoir for viral replication and spread to cardiac myocytes. These studies provide the first indication of an integrated network of cell-type-specific innate immune components for organ protection.

scholarly journals Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production

Diabetologia ◽  
2016 ◽  
Vol 59 (9) ◽  
pp. 1938-1947 ◽  
Author(s):  
Francesca Semplici ◽  
Angeles Mondragon ◽  
Benedict Macintyre ◽  
Katja Madeyski-Bengston ◽  
Anette Persson-Kry ◽  
...  
Keyword(s):  
Cell Type ◽  
Pas Kinase ◽  
Cell Type Specific ◽  
Specific Deletion

scholarly journals The Cell Type–Specific Functions of miR-21 in Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Beibei Dai ◽  
Feng Wang ◽  
Xiang Nie ◽  
Hengzhi Du ◽  
Yanru Zhao ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular System ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Cell Type ◽  
Physiological Processes ◽  
A Cell ◽  
Cell Type Specific ◽  
Underlying Mechanisms ◽  
Endothelial Nitric Oxide

Cardiovascular diseases are one of the prime reasons for disability and death worldwide. Diseases and conditions, such as hypoxia, pressure overload, infection, and hyperglycemia, might initiate cardiac remodeling and dysfunction by inducing hypertrophy or apoptosis in cardiomyocytes and by promoting proliferation in cardiac fibroblasts. In the vascular system, injuries decrease the endothelial nitric oxide levels and affect the phenotype of vascular smooth muscle cells. Understanding the underlying mechanisms will be helpful for the development of a precise therapeutic approach. Various microRNAs are involved in mediating multiple pathological and physiological processes in the heart. A cardiac enriched microRNA, miR-21, which is essential for cardiac homeostasis, has been demonstrated to act as a cell–cell messenger with diverse functions. This review describes the cell type–specific functions of miR-21 in different cardiovascular diseases and its prospects in clinical therapy.

scholarly journals Cell type‐specific mechanisms coupling protease‐activated receptor‐1 to infectious colitis pathogenesis

2019 ◽  
Vol 18 (1) ◽  
pp. 91-103
Author(s):  
Alexander A. Boucher ◽  
Leah Rosenfeldt ◽  
Duaa Mureb ◽  
Jessica Shafer ◽  
Bal Krishan Sharma ◽  
...  
Keyword(s):  
Cell Type ◽  
Infectious Colitis ◽  
Cell Type Specific ◽  
Protease Activated Receptor 1

The role of p300 proteins in cyclic AMP-mediated cell type-specific apoptosis in cardiac myocytes

1998 ◽  
Vol 4 (3) ◽  
pp. 78
Author(s):  
Koji Hasegawa ◽  
Eri Iwai-Kanai ◽  
Makoto Araki ◽  
Tatsuya Morimoto ◽  
Tsuyoshi Kakita ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Cardiac Myocytes ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals The contribution of astrocyte and neuronal Panx1 to seizures is model and brain region dependent

2021 ◽  
Author(s):  
Price Obot ◽  
Libor Velíšek ◽  
Jana Velíšková ◽  
Eliana Scemes
Keyword(s):  
Brain Region ◽  
Power Spectra ◽  
Cortical Region ◽  
Cell Type ◽  
Epileptiform Discharges ◽  
Seizure Models ◽  
Cell Type Specific ◽  
Specific Deletion

AbstractPannexin1 (Panx1) is an ATP release channel expressed in neurons and astrocytes that plays important roles in CNS physiology and pathology. Evidence for the involvement of Panx1 in seizures includes the reduction of epileptiform activity and ictal discharges following Panx1 channel blockade or deletion. However, very little is known about the relative contribution of astrocyte and neuronal Panx1 channels to hyperexcitability. To this end, mice with global and cell type specific deletion of Panx1 were used in one in vivo and two in vitro seizure models. In the low-Mg2+in vitro model, global deletion but not cell-type specific deletion of Panx1 reduced the frequency of epileptiform discharges. This reduced frequency of discharges did not impact the overall power spectra obtained from local field potentials. In the in vitro KA model, in contrast, global or cell type specific deletion of Panx1 did not affect the frequency of discharges, but reduced the overall power spectra. EEG recordings following KA-injection in vivo revealed that although global deletion of Panx1 did not affect the onset of status epilepticus (SE), SE onset was delayed in mice lacking neuronal Panx1 and accelerated in mice lacking astrocyte Panx1. EEG power spectral analysis disclosed a Panx1-dependent cortical region effect; while in the occipital region, overall spectral power was reduced in all three Panx1 genotypes; in the frontal cortex, the overall power was not affected by deletion of Panx1. Together, our results show that the contribution of Panx1 to ictal activity is model, cell-type and brain region dependent.

Na+,K+-ATPase as a Target for Treatment of Tissue Fibrosis

2019 ◽  
Vol 26 (3) ◽  
pp. 564-575 ◽  
Author(s):  
Sergei N. Orlov ◽  
Jennifer La ◽  
Larisa V. Smolyaninova ◽  
Nickolai O. Dulin
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Lung Fibroblasts ◽  
In Vivo Studies ◽  
Myofibroblast Differentiation ◽  
Cell Type ◽  
Tissue Fibrosis ◽  
Cell Type Specific ◽  
Cox 2

Myofibroblast activation is a critical process in the pathogenesis of tissue fibrosis accounting for 45% of all deaths. No effective therapies are available for the treatment of fibrotic diseases. We focus our mini-review on recent data showing that cardiotonic steroids (CTS) that are known as potent inhibitors of Na+,K+-ATPase affect myofibroblast differentiation in a cell type-specific manner. In cultured human lung fibroblasts (HLF), epithelial cells, and cancer-associated fibroblasts, CTS blocked myofibroblast differentiation triggered by profibrotic cytokine TGF-β. In contrast, in the absence of TGF-β, CTS augmented myofibroblast differentiation of cultured cardiac fibroblasts. The cell type-specific action of CTS in myofibroblast differentiation is consistent with data obtained in in vivo studies. Thus, infusion of ouabain via osmotic mini-pumps attenuated the development of lung fibrosis in bleomycintreated mice, whereas marinobufagenin stimulated renal and cardiac fibrosis in rats with experimental renal injury. In TGF-β-treated HLF, suppression of myofibroblast differentiation by ouabain is mediated by elevation of the [Na+]i/[K+]i ratio and is accompanied by upregulation of cyclooxygenase COX-2 and downregulation of TGF-β receptor TGFBR2. Augmented expression of COX-2 is abolished by inhibition of Na+/Ca2+ exchanger, suggesting a key role of [Ca2+]i-mediated signaling. What is the relative impact in tissue fibrosis of [Na+]i,[K+]iindependent signaling documented in several types of CTS-treated cells? Do the different conformational transitions of Na+,K+-ATPase α1 subunit in the presence of ouabain and marinobufagenin contribute to their distinct involvement in myofibroblast differentiation? Additional experiments should be done to answer these questions and to develop novel pharmacological approaches for the treatment of fibrosis-related disorders.

scholarly journals α- and β-Adrenergic Pathways Differentially Regulate Cell Type–Specific Apoptosis in Rat Cardiac Myocytes

Circulation ◽  
1999 ◽  
Vol 100 (3) ◽  
pp. 305-311 ◽  
Author(s):  
Eri Iwai-Kanai ◽  
Koji Hasegawa ◽  
Makoto Araki ◽  
Tsuyoshi Kakita ◽  
Tatsuya Morimoto ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Cell Type ◽  
Cell Type Specific ◽  
Rat Cardiac Myocytes

General or Cell Type-Specific Deletion and Replacement of Connexin-Coding DNA in the Mouse

Methods ◽  
2000 ◽  
Vol 20 (2) ◽  
pp. 205-218 ◽  
Author(s):  
Martin Theis ◽  
Thomas M. Magin ◽  
Achim Plum ◽  
Klaus Willecke
Keyword(s):  
Cell Type ◽  
Cell Type Specific ◽  
Specific Deletion
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