scholarly journals Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 322 ◽  
Author(s):  
Juan E. Camacho Londoño ◽  
André Marx ◽  
Axel E. Kraft ◽  
Alexander Schürger ◽  
Christin Richter ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Cardiac Cells ◽  
Trpc Channels ◽  
Entry Pathway ◽  
Adult Mice ◽  
Crac Channels ◽  
Induced Changes ◽  
Trpc Proteins

TRPC proteins form cation conducting channels regulated by different stimuli and are regulators of the cellular calcium homeostasis. TRPC are expressed in cardiac cells including cardiac fibroblasts (CFs) and have been implicated in the development of pathological cardiac remodeling including fibrosis. Using Ca2+ imaging and several compound TRPC knockout mouse lines we analyzed the involvement of TRPC proteins for the angiotensin II (AngII)-induced changes in Ca2+ homeostasis in CFs isolated from adult mice. Using qPCR we detected transcripts of all Trpc genes in CFs; Trpc1, Trpc3 and Trpc4 being the most abundant ones. We show that the AngII-induced Ca2+ entry but also Ca2+ release from intracellular stores are critically dependent on the density of CFs in culture and are inversely correlated with the expression of the myofibroblast marker α-smooth muscle actin. Our Ca2+ measurements depict that the AngII- and thrombin-induced Ca2+ transients, and the AngII-induced Ca2+ entry and Ca2+ release are not affected in CFs isolated from mice lacking all seven TRPC proteins (TRPC-hepta KO) compared to control cells. However, pre-incubation with GSK7975A (10 µM), which sufficiently inhibits CRAC channels in other cells, abolished AngII-induced Ca2+ entry. Consequently, we conclude the dispensability of the TRPC channels for the acute neurohumoral Ca2+ signaling evoked by AngII in isolated CFs and suggest the contribution of members of the Orai channel family as molecular constituents responsible for this pathophysiologically important Ca2+ entry pathway.

scholarly journals TRPC Channels in the SOCE Scenario

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 126 ◽  
Author(s):  
Jose J. Lopez ◽  
Isaac Jardin ◽  
Jose Sanchez-Collado ◽  
Ginés M. Salido ◽  
Tarik Smani ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cell Types ◽  
Trpc Channels ◽  
Crac Channels ◽  
Relevant Role ◽  
Transient Receptor ◽  
Trpc Proteins ◽  
Soc Channels

Transient receptor potential (TRP) proteins form non-selective Ca2+ permeable channels that contribute to the modulation of a number of physiological functions in a variety of cell types. Since the identification of TRP proteins in Drosophila, it is well known that these channels are activated by stimuli that induce PIP2 hydrolysis. The canonical TRP (TRPC) channels have long been suggested to be constituents of the store-operated Ca2+ (SOC) channels; however, none of the TRPC channels generate Ca2+ currents that resemble ICRAC. STIM1 and Orai1 have been identified as the components of the Ca2+ release-activated Ca2+ (CRAC) channels and there is a body of evidence supporting that STIM1 is able to gate Orai1 and TRPC1 in order to mediate non-selective cation currents named ISOC. STIM1 has been found to interact to and activate Orai1 and TRPC1 by different mechanisms and the involvement of TRPC1 in store-operated Ca2+ entry requires both STIM1 and Orai1. In addition to the participation of TRPC1 in the ISOC currents, TRPC1 and other TRPC proteins might play a relevant role modulating Orai1 channel function. This review summarizes the functional role of TRPC channels in the STIM1–Orai1 scenario.

scholarly journals IGF-1 protects against angiotensin II-induced cardiac fibrosis by targeting αSMA

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Sangmi Ock ◽  
Woojin Ham ◽  
Chae Won Kang ◽  
Hyun Kang ◽  
Wang Soo Lee ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mechanisms ◽  
Low Dose ◽  
Cardiac Fibrosis ◽  
Interstitial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Coiled Coil ◽  
Proliferation And Differentiation

AbstractThe insulin-like growth factor 1 receptor (IGF-1R) signaling in cardiomyocytes is implicated in physiological hypertrophy and myocardial aging. Although fibroblasts account for a small amount of the heart, they are activated when the heart is damaged to promote cardiac remodeling. However, the role of IGF-1R signaling in cardiac fibroblasts is still unknown. In this study, we investigated the roles of IGF-1 signaling during agonist-induced cardiac fibrosis and evaluated the molecular mechanisms in cultured cardiac fibroblasts. Using an experimental model of cardiac fibrosis with angiotensin II/phenylephrine (AngII/PE) infusion, we found severe interstitial fibrosis in the AngII/PE infused myofibroblast-specific IGF-1R knockout mice compared to the wild-type mice. In contrast, low-dose IGF-1 infusion markedly attenuated AngII-induced cardiac fibrosis by inhibiting fibroblast proliferation and differentiation. Mechanistically, we demonstrated that IGF-1-attenuated AngII-induced cardiac fibrosis through the Akt pathway and through suppression of rho-associated coiled-coil containing kinases (ROCK)2-mediated α-smooth muscle actin (αSMA) expression. Our study highlights a novel function of the IGF-1/IGF-1R signaling in agonist-induced cardiac fibrosis. We propose that low-dose IGF-1 may be an efficacious therapeutic avenue against cardiac fibrosis.

Force regulates smooth muscle actin in cardiac fibroblasts

2000 ◽  
Vol 279 (6) ◽  
pp. H2776-H2785 ◽  
Author(s):  
J. Wang ◽  
A. Seth ◽  
C. A. G. McCulloch
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Cultured Cells ◽  
Kinase Inhibitor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Focal Adhesions ◽  
Pressure Overload ◽  
Muscle Actin ◽  
P38 Kinase

Chronic ventricular pressure overload can regulate expression of α-smooth muscle actin (SMA) in cardiac fibroblasts, but it is unclear if force alone or the concomitant activity of angiotensin II is the principal regulatory factor. To test if SMA mRNA and protein in rat cardiac fibroblasts are regulated directly by force, we first induced SMA expression in cultured cells and then applied magnetically generated perpendicular forces through focal adhesions using collagen-coated magnetite beads. Continuous static forces (0.65 pN/μm2) selectively reduced SMA but not β-actin mRNA and protein content within 4 h (to 55 ± 9% of controls); SMA returned to baseline by 8 h. There was no change in SMA content after force application with either plasma or the cellular fibronectin IIIA domain, BSA, or poly-l-lysine beads. The early loss of SMA was apparently due to selective leakage into the cell culture medium. Treatment with angiotensin II (10 nM) abrogated the force-induced reduction of SMA and increased the levels of this protein. The stress kinase p38 was phosphorylated by force, whereas extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase were unaffected. The p38 kinase inhibitor SB-203580 relieved the force-induced SMA reduction. We conclude that force-induced inhibition of SMA is mediated through the p38 kinase pathway, and this pathway antagonizes angiotensin II regulation of SMA.

Luteolin Antagonizes Angiotensin II-Dependent Proliferation and Collagen Synthesis of Cultured rat Cardiac Fibroblasts

2015 ◽  
Vol 16 (5) ◽  
pp. 430-439 ◽  
Author(s):  
Tingting Wang ◽  
Defeng Pan ◽  
Yingying Zhang ◽  
Dongye Li ◽  
Yanbin Zhang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collagen Synthesis ◽  
Cardiac Fibroblasts

scholarly journals The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1861
Author(s):  
Jemima Seidenberg ◽  
Mara Stellato ◽  
Amela Hukara ◽  
Burkhard Ludewig ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Beclin 1 ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Background: Pathological activation of cardiac fibroblasts is a key step in development and progression of cardiac fibrosis and heart failure. This process has been associated with enhanced autophagocytosis, but molecular mechanisms remain largely unknown. Methods and Results: Immunohistochemical analysis of endomyocardial biopsies showed increased activation of autophagy in fibrotic hearts of patients with inflammatory cardiomyopathy. In vitro experiments using mouse and human cardiac fibroblasts confirmed that blockade of autophagy with Bafilomycin A1 inhibited fibroblast-to-myofibroblast transition induced by transforming growth factor (TGF)-β. Next, we observed that cardiac fibroblasts obtained from mice overexpressing transcription factor Fos-related antigen 2 (Fosl-2tg) expressed elevated protein levels of autophagy markers: the lipid modified form of microtubule-associated protein 1A/1B-light chain 3B (LC3BII), Beclin-1 and autophagy related 5 (Atg5). In complementary experiments, silencing of Fosl-2 with antisense GapmeR oligonucleotides suppressed production of type I collagen, myofibroblast marker alpha smooth muscle actin and autophagy marker Beclin-1 in cardiac fibroblasts. On the other hand, silencing of either LC3B or Beclin-1 reduced Fosl-2 levels in TGF-β-activated, but not in unstimulated cells. Using a cardiac hypertrophy model induced by continuous infusion of angiotensin II with osmotic minipumps, we confirmed that mice lacking either Fosl-2 (Ccl19CreFosl2flox/flox) or Atg5 (Ccl19CreAtg5flox/flox) in stromal cells were protected from cardiac fibrosis. Conclusion: Our findings demonstrate that Fosl-2 regulates autophagocytosis and the TGF-β-Fosl-2-autophagy axis controls differentiation of cardiac fibroblasts. These data provide a new insight for the development of pharmaceutical targets in cardiac fibrosis.

scholarly journals Angiotensin II-induced protein tyrosine phosphorylation in neonatal rat cardiac fibroblasts.

1994 ◽  
Vol 269 (30) ◽  
pp. 19626-19632
Author(s):  
W. Schorb ◽  
T.C. Peeler ◽  
N.N. Madigan ◽  
K.M. Conrad ◽  
K.M. Baker
Keyword(s):  
Angiotensin Ii ◽  
Tyrosine Phosphorylation ◽  
Cardiac Fibroblasts ◽  
Neonatal Rat ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

PPARβ/δ activation inhibits angiotensin II-induced collagen type I expression in rat cardiac fibroblasts

2007 ◽  
Vol 460 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Huijie Zhang ◽  
Rongbiao Pi ◽  
Ruifang Li ◽  
Ping Wang ◽  
Futian Tang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Type I
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