Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop DOI Creative Commons
Jiahao He, Xinwei Cheng, Bin Fang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 24, 2024

Abstract Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused fibrotic disorders skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin and drives its progression promoting fibroblasts activation. However, how influences activation for remains unknown. Here, we report positive feedback loop mediated mechanosensitive ion channel Piezo1 aberrant tissue mechanics in driving fibrosis. upregulated both humans mice. knockdown dermal lose their fibroproliferative phenotypes despite being grown on stiffer substrate. We show acts through Wnt2/Wnt11 pathway to mechanically induce secretion C-C motif chemokine ligand 24 (CCL24, also known eotaxin-2), potent cytokine associated with disorders. Importantly, adeno-associated virus (AAV)-mediated ameliorated Overall, increased promotes inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. turn, microenvironment increases expression exacerbate aggression. Therefore, targeting represents strategy break between mechanotransduction

Language: Английский

Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments DOI Creative Commons
Zhennan Yuan, Yingpu Li, Sifan Zhang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Language: Английский

Citations

368
SARS-CoV-2, COVID-19 and the aging immune system DOI Creative Commons
Juliet M. Bartleson, Dina Radenković, Anthony J. Covarrubias

et al.

Nature Aging, Journal Year: 2021, Volume and Issue: 1(9), P. 769 - 782

Published: Sept. 14, 2021

Language: Английский

Citations

288
Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy DOI Creative Commons
Yangfu Jiang, Hongying Zhang, Jiao Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 24, 2022

Abstract Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor stromal cells to promote proliferation, migration, invasion, angiogenesis immune evasion. Both ECM itself stiffening-induced mechanical stimuli may activate cell membrane receptors mechanosensors such as integrin, Piezo1 TRPV4, thereby modulating the malignant phenotype of cells. A better understanding how stiffness regulates progression will contribute development new therapeutics. rapidly expanding evidence in this research area suggests that regulators effectors represent potential therapeutic targets cancer. This review summarizes recent work on regulation cancer, effects progression, immunity drug resistance. We also discuss be druggable intervene Based these advances, future efforts can made develop more effective safe drugs interrupt stiffness-induced oncogenic signaling,

Language: Английский

Citations

262
Tuning immunity through tissue mechanotransduction DOI Open Access
Huixun Du, Juliet M. Bartleson, Sergei Butenko

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 174 - 188

Published: Aug. 16, 2022

Language: Английский

Citations

227
Chronic inflammation and the hallmarks of aging DOI Creative Commons
Jordan J. Baechle, Nan Chen, Priya Makhijani

et al.

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

Citations

153
Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance DOI
Patrizia Romani,

Nunzia Nirchio,

Mattia Arboit

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(2), P. 168 - 180

Published: Feb. 1, 2022

Language: Английский

Citations

138
Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer’s disease DOI Creative Commons
Jin Hu, Qiang Chen, Hongrui Zhu

et al.

Neuron, Journal Year: 2022, Volume and Issue: 111(1), P. 15 - 29.e8

Published: Nov. 10, 2022

Language: Английский

Citations

93
Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells DOI Creative Commons
Juraj Adamik, Paul V. Munson, Felix J. Hartmann

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 2, 2022

Abstract Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic biology and their ability to orchestrate responses is poorly developed. Here, we map single-cell states profiles inflammatory tolerogenic monocytic cells using recently developed multiparametric approaches. Single-cell pathway activation scores reveal simultaneous engagement multiple pathways distinct differentiation stages. GM-CSF/IL4-induce rapid reprogramming glycolytic monocytes transient co-activation mitochondrial followed by TLR4-dependent maturation cells. Skewing the mTOR:AMPK phosphorylation balance upregulation OXPHOS, fatty acid oxidation underpin hyperactivity an immunosuppressive phenotype cells, which exhibit maturation-resistance a de-differentiated marked unique immunoregulatory receptor signatures. This dataset provides important insights into impacting

Language: Английский

Citations

72
Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy DOI Creative Commons
Yufeng Shou,

Xin Yong Teo,

Kenny Zhuoran Wu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(21)

Published: April 29, 2023

Abstract Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, time. Compared to such as stiffness, porosity, topography, the current understanding on effects stimulations cells remains limited, attributing lack access devices, complexity experimental set‐up, data interpretation. Yet, in pursuit emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial understand how respond variety forces are omnipresent vivo so they can be exploited enhance therapeutic outcomes. With rising appreciation extracellular matrix (ECM) key regulator biofunctions, researchers have bioengineered suite ECM‐mimicking hydrogels, which fine‐tuned spatiotemporal cues model complex profiles. This review first discusses stimuli may impact different cellular components various mechanobiology pathways involved. Then, hydrogels designed incorporate parameters influence behaviors described. The Scopus database also used analyze relative strength evidence, ranging from strong weak, based number published literatures, associated citations, treatment significance. Additionally, impacts clinically relevant types including mesenchymal stem cells, fibroblasts, immune evaluated. aim draw attention paucity studies well highlight potential using cocktail intensities fates (similar concept biochemical direct fate). It envisioned this progress report will inspire more exciting development mechanoresponsive biomedical applications.

Language: Английский

Citations

51
Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing DOI Creative Commons
Sergei Butenko, Raji R. Nagalla, Christian F. Guerrero‐Juarez

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 9, 2024

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior healing in female mice. We observe that softer, lightly crosslinked promote greater cellular infiltration result smaller scars compared stiffer, heavily hydrogels. Using single-cell RNA sequencing, we further show increase inflammation lead the formation a distinct macrophage subpopulation exhibiting signs oxidative activity fusion. Conversely, are more readily taken up by macrophages integrated within tissue. The physical properties differentially affect fibroblast interactions, promoting pro-fibrotic drives fusion through RANKL signaling. These findings suggest tuning can guide responses improve healing, offering insights for designing better biomaterials treatment.

Language: Английский

Citations

36