βIV-Spectrin in Cardiac Fibroblasts: Implications for Fibrosis and Therapeutic Targeting in Cardiac Diseases. Comment on Nassal et al. Spectrin-Based Regulation of Cardiac Fibroblast Cell-Cell Communication. Cells 2023, 12, 748 DOI Creative Commons

Wenjing Xiang,

Ning Zhou, Lei Li

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(17), P. 2186 - 2186

Published: Aug. 31, 2023

Fibroblasts in the heart, traditionally recognized as interstitial cells, have long been overlooked study of cardiac physiology and pathology [...].

Language: Английский

Mechanosensing by Piezo1 and its implications in the kidney DOI
Xi Yuan, X Zhao, Weidong Wang

et al.

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(6)

Published: April 29, 2024

Abstract Piezo1 is an essential mechanosensitive transduction ion channel in mammals. Its unique structure makes it capable of converting mechanical cues into electrical and biological signals, modulating (patho)physiological processes a wide variety cells. There increasing evidence demonstrating that the piezo1 plays vital role renal physiology disease conditions. This review summarizes current on properties Piezo1, gating modulation, pharmacological characteristics, with special focus distribution significance kidney, which may provide insights potential treatment targets for diseases involving this channel.

Language: Английский

Citations

4

Ca2+ Signaling in Cardiac Fibroblasts: An Emerging Signaling Pathway Driving Fibrotic Remodeling in Cardiac Disorders DOI Creative Commons
Francesco Moccia, Antonio Totaro, Germano Guerra

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 734 - 734

Published: March 17, 2025

Cardiac fibrosis is a scarring event that occurs in the myocardium response to multiple cardiovascular disorders, such as acute myocardial infarction (AMI), ischemic cardiomyopathy, dilated hypertensive heart disease, inflammatory diabetic and aortic stenosis. Fibrotic remodeling mainly sustained by differentiation of fibroblasts into myofibroblasts, which synthesize secrete most extracellular matrix (ECM) proteins. An increase intracellular Ca2+ concentration ([Ca2+]i) cardiac emerging critical mediator fibrogenic signaling cascade. Herein, we review mechanisms may shape signals involved fibroblast transdifferentiation myofibroblasts. We focus our attention on functional interplay between inositol-1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) store-operated entry (SOCE). In accordance with this, InsP3Rs SOCE drive elicited Gq-protein coupled (GqPCRs) promote fibrotic remodeling. Then, describe additional sustain entry, including receptor-operated (ROCE), P2X receptors, Transient Receptor Potential (TRP) channels, Piezo1 channels. parallel, discuss pharmacological manipulation handling machinery promising approach mitigate or reverse disorders.

Language: Английский

Citations

0

RNA-sequencing demonstrates transcriptional differences between human vocal fold fibroblasts and myofibroblasts DOI Creative Commons
Michelle Bretl,

Lingxin Cheng,

Christina Kendziorski

et al.

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 7, 2025

Differentiation of fibroblasts into myofibroblasts is necessary for wound healing, but excessive myofibroblast presence and persistence can result in scarring. Treatment scarring limited largely due to a lack comprehensive understanding how differ at the transcript level. The purpose this study was characterize transcriptional profiles injured relative normal fibroblasts, utilizing from vocal fold as model. Utilizing bulk RNA sequencing technology, we identified differentially expressed genes between four cell lines (cVFF), one line scarred (sVFF), treated with transforming growth factor-beta 1 (TGF-β1), representing an induced-scar phenotype (tVFF). Principal component analysis revealed clustering separate TGF-β1; were more similar than TGF-β1. Enrichment analyses pathways related signaling, receptor-ligand activity, regulation functions adhesion ECM binding Although transcriptomic TGF-β1 relatively dissimilar, most highly co-expressed enriched actin cytoskeleton binding, which supports use represent phenotype. Transcriptomics myofibroblasts, including those retrieved scar Despite large differences transcriptomics tVFF sVFF, serve useful vitro model highlight key similarities extracted pathology, well expected healthy folds.

Language: Английский

Citations

0

Contribution of the TRPM4 Channel to Osteogenic Differentiation of Human Aortic Valve Interstitial Cells DOI Creative Commons
Margaux Aize, Arthur Boilève, Benoit D. Roussel

et al.

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Background Aortic stenosis due to deleterious remodeling of the aortic valve is a health concern since it can be corrected only by replacement poor knowledge cellular mechanisms involved. Fibroblastic valvular interstitial cells (VICs) play central role in leaflet stiffness trans‐differentiation into osteoblast‐like leading calcification. The TRPM4 (transient receptor potential melastatin 4) cation channel was shown participate cardiac fibroblast remodeling. It also involved radiation‐induced vivo mice. We hypothesized that might human VIC transition osteoblastic phenotype. Methods Human valves were collected from patients undergoing surgical replacement. Isolated VICs maintained 14 days culture standard or pro‐calcifying media and submitted inhibitor 9‐phenanthrol, small hairpin RNA–TRPM4. Osteogenic differentiation evaluated measuring hydroxyapatite crystals Alizarin red staining protein expression osteogenic markers. Results Western blot on revealed functionality confirmed patch‐clamp recordings exhibiting cationic current sensitive voltage internal Ca 2+ . exhibited higher mineralization than media, with an increase Mineralization markers (bone morphogenetic 2, runt‐related transcription factor 2) decreased when contained 9‐phenanthrol Similarly, SMAD1/5 nuclear activated T‐cell pathways stimulated conditions compared but reduced Conclusions participates thus appears as target prevent

Language: Английский

Citations

0

Characterization and differentiation of myocardial remodeling using artificial intelligence‐assisted confocal Raman spectroscopy imaging DOI Creative Commons

Ruopu Song,

Xiaolong Yin,

Manlin Zhu

et al.

View, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Myocardial remodeling is a crucial pathophysiological factor underlying heart failure, the leading cause of death globally. In this study, we utilized confocal Raman spectroscopy imaging to gain unprecedented insights into myocardial tissue during remodeling. We induced in rats via subcutaneous administration isoproterenol (ISO) (5 mg/kg) over seven days, meticulously validated by echocardiography and histopathological staining. Subsequent analyses using transmission electron microscopy revealed significant mitochondrial damage. Confocal imaging, however, provided most detailed visualization complex architecture within remodeled tissue. Notably, technique enabled precise differentiation between hypertrophic fibrotic regions myocardium. These findings not only deepen our understanding mechanisms driving but also highlight transformative potential as label‐free, high‐resolution tool for assessing cardiac pathology. Additionally, artificial intelligence (AI) assisted identification rapid sites tissues further enhance technology targeted clinical applications, marking advancement managing failure.

Language: Английский

Citations

0

Insights into the post-translational modifications in heart failure DOI
Xudong Zhang, Yan Wang, Huaping Li

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102467 - 102467

Published: Aug. 25, 2024

Language: Английский

Citations

3

The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions DOI
Shasha Wu,

Q. Chen,

Xiao Yang

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111730 - 111730

Published: March 1, 2025

Language: Английский

Citations

0

Epigenetic Regulation of Fibroblasts and Crosstalk between Cardiomyocytes and Non-Myocyte Cells in Cardiac Fibrosis DOI Creative Commons

Liangyu Chu,

Daihan Xie,

Dachun Xu

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(9), P. 1382 - 1382

Published: Sept. 12, 2023

Epigenetic mechanisms and cell crosstalk have been shown to play important roles in the initiation progression of cardiac fibrosis. This review article aims provide a thorough overview epigenetic involved fibroblast regulation. During fibrosis, regulation encompasses multitude mechanisms, including DNA methylation, histone acetylation chromatin remodeling. These regulate phenotype fibroblasts extracellular matrix composition by modulating gene expression, thereby orchestrating Moreover, fibrosis disrupts normal function imposing myocardial mechanical stress compromising electrical conduction. also delves into intricate between cardiomyocytes non-cardiomyocytes heart. A comprehensive understanding governing is critical for development effective therapeutic strategies. Further research warranted unravel precise molecular underpinning these processes identify potential targets.

Language: Английский

Citations

9

Mechanotransductive receptor Piezo1 as a promising target in the treatment of fibrosis diseases DOI Creative Commons

Yi Xu,

Yiqian Huang,

Xiaoqing Cheng

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 12, 2023

Fibrosis could happen in every organ, leading to organic malfunction and even organ failure, which poses a serious threat global health. Early treatment of fibrosis has been reported be the turning point, therefore, exploring potential correlates pathogenesis how reverse become pressing issue. As mechanism-sensitive cationic calcium channel, Piezo1 turns on response changes lipid bilayer plasma membrane. exerts multiple biological roles, including inhibition inflammation, cytoskeletal stabilization, epithelial-mesenchymal transition, stromal stiffness, immune cell mechanotransduction, interestingly enough. These processes are closely associated with development fibrotic diseases. Recent studies have shown that deletion or knockdown attenuates onset fibrosis. Therefore, this paper we comprehensively describe biology gene, focusing its relevance pulmonary fibrosis, renal pancreatic cardiac diseases, except for role drugs (agonists), increased intracellular mechanical stress using gene alleviating

Language: Английский

Citations

8

Mechanism of sodium butyrate, a metabolite of gut microbiota, regulating cardiac fibroblast transdifferentiation via the NLRP3/Caspase-1 pyroptosis pathway DOI Creative Commons

Tiancheng Dong,

Dingkao Huang,

Zhengzheng Jin

et al.

Journal of Cardiothoracic Surgery, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 15, 2024

Abstract Background Cardiac fibroblasts (CFs) are activated after initial injury, and then differentiate into myofibroblasts (MFs), which play a pivotal role as the primary mediator cells in pathological remodeling. Sodium butyrate (NaB), being metabolite of gut microbiota, exhibits anti-inflammatory property local therapies on sites other than intestine. Thus, this study aimed to probe mechanism by NaB regulates CFs transdifferentiation through NLRP3/Caspase-1 pyroptosis pathway. Methods were cultured vitro induced MFs TGFβ1. identified immunofluorescence labelling technique vimentin α-SMA, followed treatment with or NLRP3 inflammasome inhibitor (CY-09) its activator [nigericin sodium salt (NSS)]. The expression levels GSDMD-N/NLRP3/cleaved Caspase-1 proteins, inflammatory factors IL-1β/IL-18/IL-6/IL-10 determined using immunofluorescence, Western blot ELISA. Cell proliferation migration evaluated CCK-8 assay cell scratch test, respectively. Results Following induction TGFβ1, exhibited increased α-SMA proteins IL-6/IL-10, well proliferative migratory abilities. TGFβ1 MFs, while inhibited differentiation. inactivated CY-09 demonstrated inhibitory effects pathway, leading reduction TGFβ1-induced transdifferentiation. NSS thus partially counteracting effect intestinal microbiota Conclusion NaB, activation pathway CFs, repressed MFs.

Language: Английский

Citations

2