IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice DOI Creative Commons

Bang wei Wu,

Qingyu Huang,

Tongqing Chen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Abstract Background Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities the heart ultimately evolves failure. Currently, treatment options for DCM remain limited. IL-37 exerts substantial influence on regulation inflammation metabolism. Whether is involved in unknown. Methods The plasma samples were collected from healthy controls, diabetic patients patients, level its relationship with function observed. changes cardiac function, myocardial fibrosis mitochondrial injury mice or without intervention investigated vivo. By an vitro co-culture approach involving HG challenge cardiomyocytes fibroblasts, interaction carried out by fibroblast profibrotic activation was studied. Finally, possible interactive mediator between fibroblasts explored, role relevant molecular mechanisms. Results We showed that upregulated compared controls patients. Both recombinant administration inducing expression alleviated dysfunction mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting significant cardiomyocyte apoptosis release extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling cGAS-STING pathway initiate pro-fibrotic process adverse remodeling. However, presence ameliorated preserving activity SIRT1-AMPK-PGC1α axis, reduction vesicle attenuating progression DCM. Conclusions Collectively, our study demonstrates protective DCM, offering promising therapeutic agent this disease.

Language: Английский

Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis DOI Creative Commons

Haohui Lin,

Xia Wang, Manhon Chung

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 27, 2025

Direct reprogramming has garnered considerable attention due to its capacity directly convert differentiated cells into desired cells. Fibroblasts are frequently employed in studies their abundance and accessibility. However, they also the key drivers progression of fibrosis, a pathological condition characterized by excessive extracellular matrix deposition tissue scarring. Furthermore, initial stage typically involves deactivating fibrotic pathways. Hence, direct offers valuable method regenerate target for repair while simultaneously reducing tendencies. Understanding link between fibrosis could help develop effective strategies treat damaged with potential risk fibrosis. This review summarizes advances reveals anti-fibrosis effects various organs such as heart, liver, skin. we dissect mechanisms influenced molecules including TGF-β signaling, mechanical inflammation epigenetic modifiers, metabolic regulators. Innovative methods fibroblast like small molecules, CRISPRa, modified mRNA, challenges cellular heterogeneity senescence faced vivo reprogramming, discussed.

Language: Английский

Citations

1
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis DOI Open Access
Margherita Sisto, Sabrina Lisi

Published: Jan. 3, 2024

Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often the evolution pathological conditions, causes organ failure, and can, in extreme cases, compromises functionality organs to point causing death. In recent years, considerable efforts have been made understand molecular mechanisms underlying fibrotic identify possible therapeutic strategies. Great interest has aroused discovery association between epithelial mesenchymal plasticity (EMP), particular transition (EMT), fibrogenesis, which led identification complex closely interconnected with each other, could explain EMT-dependent fibrosis. However, result remains unsatisfactory from view. advances epigenetics, is based on chromatin remodeling through various histone modifications or intervention non-coding RNAs (ncRNAs), provided more information process, this represent promising path forward for innovative strategies review, we summarize current research epigenetic involved fibrosis, focus regulation EMP/EMT-dependent

Language: Английский

Citations

4
The Impact of Natriuretic Peptides on Heart Development, Homeostasis, and Disease DOI Creative Commons

Alexandra E. Giovou,

Monika M Gladka, Vincent M. Christoffels

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 931 - 931

Published: May 28, 2024

During mammalian heart development, the clustered genes encoding peptide hormones, Natriuretic Peptide A (NPPA; ANP) and B (NPPB; BNP), are transcriptionally co-regulated co-expressed predominately in atrial ventricular trabecular cardiomyocytes. After birth, expression of NPPA a natural antisense transcript NPPA-AS1 becomes restricted to Both NPPB induced by cardiac stress serve as markers for cardiovascular dysfunction or injury. gene products extensively used diagnostic prognostic biomarkers various disorders. Membrane-localized guanylyl cyclase receptors on many cell types throughout body mediate signaling natriuretic ligands through generation intracellular cGMP, which interacts with modulates activity cGMP-activated kinase other enzymes ion channels. The system plays fundamental role cardio-renal homeostasis, its potent diuretic vasodilatory effects provide compensatory mechanisms pathophysiological conditions failure. In addition, both peptides, but also CNP, have important intracardiac actions during development homeostasis independent systemic functions. Exploration functions may new leads therapeutic utility peptide-mediated diseases rhythm Here, we review recent insights into regulation disease.

Language: Английский

Citations

4
Extracellular Matrix Stiffness: Mechanotransduction and Mechanobiological Response-Driven Strategies for Biomedical Applications Targeting Fibroblast Inflammation DOI Open Access
Watcharaphol Tiskratok, Nontawat Chuinsiri, Phoonsuk Limraksasin

et al.

Polymers, Journal Year: 2025, Volume and Issue: 17(6), P. 822 - 822

Published: March 20, 2025

The extracellular matrix (ECM) is a dynamic network providing mechanical and biochemical cues that regulate cellular behavior. ECM stiffness critically influences fibroblasts, the primary producers, particularly in inflammation fibrosis. This review explores role of fibroblast-driven tissue remodeling, focusing on physicochemical biological mechanisms involved. Engineered materials, hydrogels, polydimethylsiloxane (PDMS) are highlighted for replicating tissue-specific stiffness, enabling precise control over cell–matrix interactions. surface functionalization substrate including collagen, polydopamine, fibronectin, enhances bioactivity fibroblast adhesion. Key mechanotransduction pathways, such as integrin signaling YAP/TAZ activation, related to regulating behaviors inflammatory responses. fibroblasts driving chronic diseases emphasizes their therapeutic potentials. Advances ECM-modifying strategies, tunable biomaterials hydrogel-based therapies, explored applications engineering, drug delivery, anti-inflammatory treatments, diagnostic tools accurate diagnosis prognosis stiffness-related diseases. integrates mechanobiology with biomedical innovations, comprehensive responses outlining future directions targeted therapies.

Language: Английский

Citations

0
The epigenetic regulation of crosstalk between cardiac fibroblasts and other cardiac cell types during stress DOI Creative Commons
Lindsay Kraus,

Salim Fredericks,

Katelyn Scheeler

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 8, 2025

With the global impact of cardiovascular disease, there is a dire need to understand mechanisms in heart during injury and stress. It has been shown that regulation extracellular matrix via cardiac fibroblasts plays major role progression failure worsening function heart. Importantly, it suggested crosstalk between other cells like cardiomyocytes, immune cells, endothelial are influenced by pathological fibroblasts. This decline across all seemingly irreversible. However, epigenetic have regulate functionality improve outcomes stress or injury. also control communication different cell types influence multiple The goal this review summarize discuss current research subsequent with disease states.

Language: Английский

Citations

0
IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice DOI Creative Commons
Qingyu Huang,

Tongqing Chen,

Jian Li

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 24, 2024

Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities the heart ultimately evolves failure. IL-37 exerts substantial influence on regulation inflammation metabolism. Whether is involved in DCM unknown.

Language: Английский

Citations

3
Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases DOI Creative Commons
Sumra Komal, Yuan Gao,

Zhi-Mo Wang

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1353 - 1353

Published: Oct. 10, 2024

Myocardial fibroblasts play a crucial role in heart structure and function. In recent years, significant progress has been made understanding the epigenetic regulation of myocardial fibroblasts, which is essential for cardiac development, homeostasis, disease progression. healthy hearts, (CFs) synthesizing extracellular matrix (ECM) when dormant state. However, under pathological environmental stress, CFs transform into activated known as myofibroblasts. These myofibroblasts produce an excess ECM, promotes fibrosis. Although multiple molecular mechanisms are associated with CF activation dysfunction, emerging evidence highlights involvement this process. Epigenetics refers to heritable changes gene expression that occur without altering DNA sequence. have emerged key regulators fibroblast This review focuses on advancements emphasizes impact modifications activation. Furthermore, we present perspectives prospects future research their implications fibroblasts.

Language: Английский

Citations

3
Rap2a promotes cardiac fibrosis and exacerbates myocardial infarction through the TNIK/Merlin/YAP axis DOI Creative Commons

Zhibin Lang,

Xiaozhen Fan,

Lin Qiu

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: May 7, 2025

Myocardial fibrosis constitutes the primary pathological characteristic of myocardial infarction (MI). The activation and proliferation fibroblasts serve as crucial factors in process development myocardium. Our research delved into role that Rap2a plays cardiac function well fibrosis, while its effects on cardial (CFs) proliferation, migration, phenotypic transformation were also explored. Examination GEO database showed a notable increase expression within tissue from mice with MI compared to normal mice. deficiency relieves restrains transition, migration CFs. absence mitigates Besides, it curbs growth CFs, restricts their movement, prevents them undergoing conversion. can bind TNIK enhance expression; Merlin/YAP signaling pathway was assessed downstream target further elucidate regulatory mechanism through which influences cardiomyocytes. In conclusion, this study provides evidence promotes mediating myofibroblast transformation, CFs via TNIK/Merlin/YAP pathway, thereby exacerbating symptoms infarction.

Language: Английский

Citations

0
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis DOI Open Access
Margherita Sisto, Sabrina Lisi

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2775 - 2775

Published: Feb. 28, 2024

Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often the evolution pathological conditions, causes organ failure, and can, in extreme cases, compromise functionality organs to point causing death. In recent years, considerable efforts have been made understand molecular mechanisms underlying fibrotic identify possible therapeutic strategies. Great interest has aroused discovery association between epithelial mesenchymal plasticity (EMP), particular transition (EMT), fibrogenesis, which led identification complex closely interconnected with each other, could explain EMT-dependent fibrosis. However, result remains unsatisfactory from view. advances epigenetics, based on chromatin remodeling through various histone modifications or intervention non-coding RNAs (ncRNAs), provided more information process, this represent promising path forward for innovative strategies review, we summarize current research epigenetic involved fibrosis, focus regulation EMP/EMT-dependent

Language: Английский

Citations

1
IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice DOI Creative Commons

Bang wei Wu,

Qingyu Huang,

Tongqing Chen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Abstract Background Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities the heart ultimately evolves failure. Currently, treatment options for DCM remain limited. IL-37 exerts substantial influence on regulation inflammation metabolism. Whether is involved in unknown. Methods The plasma samples were collected from healthy controls, diabetic patients patients, level its relationship with function observed. changes cardiac function, myocardial fibrosis mitochondrial injury mice or without intervention investigated vivo. By an vitro co-culture approach involving HG challenge cardiomyocytes fibroblasts, interaction carried out by fibroblast profibrotic activation was studied. Finally, possible interactive mediator between fibroblasts explored, role relevant molecular mechanisms. Results We showed that upregulated compared controls patients. Both recombinant administration inducing expression alleviated dysfunction mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting significant cardiomyocyte apoptosis release extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling cGAS-STING pathway initiate pro-fibrotic process adverse remodeling. However, presence ameliorated preserving activity SIRT1-AMPK-PGC1α axis, reduction vesicle attenuating progression DCM. Conclusions Collectively, our study demonstrates protective DCM, offering promising therapeutic agent this disease.

Language: Английский

Citations

0