The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes DOI Creative Commons
Johannes Heidenberger,

Raphael Hangel,

Eva I. Reihs

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 10, 2024

Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing overall chronic nature of desmopathy. A major challenge has been lack representative two-dimensional (2D) vitro models mimicking processes presence dynamic mechanical strain, both being crucial for homeostasis. Physiological levels strain exert anti-inflammatory effects, while excessive can facilitate mechanisms. Adhering 3Rs (Replacement, Reduction Refinement) principles animal research, this study aims investigate role a biomechanical environment on mechanisms by combining Flexcell culture system with primary human ligamentocytes pathology. Primary from OA patients were cultured under animal-free conditions platelet lysate, exposed either IL-1β or TGF-β3 simulate different microenvironments. Cells subjected magnitudes strain. Results showed that cells aligned along force axis This highlights critical microenvironment modulating cellular responses ligamentocyte pathology, providing valuable insights into complex interplay between stimuli cytokine signaling. These findings not only advance our understanding biology but also pave way development more targeted therapeutic strategies injuries diseases, potentially improving patient outcomes orthopedic medicine.

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
Shear-Stress Initiates Signal Two of NLRP3 Inflammasome Activation in LPS-Primed Macrophages through Piezo1 DOI
A J Fish,

James Forster,

Vaishali Malik

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

The innate immune system is tightly regulated by a complex network of chemical signals triggered pathogens, cellular damage, and environmental stimuli. While it well-established that changes in the extracellular environment can significantly influence response to pathogens damage-associated molecules, there remains limited understanding how stimuli specifically impact activation NLRP3 inflammasome, key component immunity. Here, we demonstrated shear stress act as Signal 2 inflammasome pathway treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes induce activation. We within 1.0 50 dyn/cm2 were able ASC speck formation, while was sufficient significant calcium signaling, gasdermin-D cleavage, caspase-1 activity, IL-1β secretion, all hallmarks Utilizing knockout iBMDMs, primarily activated result exposure. Quantitative polymerase chain reaction (qPCR), ELISA, small molecule inhibitor study aided us demonstrating expression Piezo1, NLRP3, gasdermin-D, IL-1β, CCL2 secretion upregulated iBMDMs treated stress. This provides foundation for further interconnected pathogenesis chronic inflammatory diseases ability play role their progression.

Language: Английский

Citations

0
Matrix stiffening induces hepatocyte functional impairment and DNA damage via the Piezo1‒ERK1/2 signaling pathway DOI

Yanan Fan,

Cheng Rui An,

Zhihui Wang

et al.

Journal of Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

Citations

0
Mechanosensitive Piezo1 channels promote neurogenic bladder fibrosis via regulating TGF-β1/Smad and Hippo/YAP1 pathways DOI

Shaoguang Feng,

Zhechen Yu,

Yicheng Yang

et al.

Experimental Cell Research, Journal Year: 2024, Volume and Issue: 442(1), P. 114218 - 114218

Published: Aug. 22, 2024

Language: Английский

Citations

2
The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling DOI Creative Commons
Xiaolin Zhang,

Tian Hai,

Cheng Xie

et al.

Channels, Journal Year: 2024, Volume and Issue: 18(1)

Published: Oct. 19, 2024

Fibrosis is usually the final pathological state of many chronic inflammatory diseases and may lead to organ malfunction. Excessive deposition extracellular matrix (ECM) molecules a characteristic most fibrotic tissues. The blood vessel wall contains three layers membrane structure, including intima, which composed endothelial cells; media, smooth muscle adventitia, formed by interaction connective tissue fibroblasts. occurrence progression vascular remodeling are closely associated with cardiovascular diseases, can alter original structure function vessel. Dysregulation composition in vessels leads continuous advancement stiffening fibrosis. Vascular fibrosis reaction excessive reduces compliance, ultimately alters key aspects biomechanics. pathogenesis vasculature strategies for its reversal have become interesting important challenges. Ion channels widely expressed system; they regulate pressure, maintain homeostasis, play roles ion transport, cell differentiation, proliferation. In vessels, different types fibroblasts, cells be relevant mediators development organs or This review discusses known potential therapeutic targets regulating repair after injury.

Language: Английский

Citations

1
Mechanisms of Fibroblast Activation during Fibrotic Tissue Remodeling DOI Creative Commons
Aleix Rius Rigau, Clara Dees

Deleted Journal, Journal Year: 2024, Volume and Issue: 2(1), P. 10002 - 10002

Published: Jan. 1, 2024

Fibrosis can occur in almost every organ system. It single organs, such as idiopathic pulmonary fibrosis (IPF), or affect multiple organs systemic sclerosis (SSc). Fibrotic diseases are recognized major cause of morbidity and mortality modern societies due to the dysfunction loss function affected organs. This is caused by progressive deposition extracellular matrix proteins released activated fibroblasts. Activation fibroblasts differentiation into myofibroblasts required for physiological tissue remodeling, e.g, during wound healing. Disruption regulatory mechanisms, however, results chronic uncontrolled activity myofibroblasts. Intensive research past years identified several core pathways pathophysiological relevance, described different fibroblast subsets based on their expression profile fibrotic tissue. Herein, we discuss molecular changes leading persistent activation remodeling with a focus lung SSc.

Language: Английский

Citations

0
Beyond Static Models: Mechanically Dynamic Matrices Reveal New Insights into Cancer and Fibrosis Progression DOI Creative Commons
Matthew Walker, Delphine Gourdon, Marco Cantini

et al.

Current Opinion in Biomedical Engineering, Journal Year: 2024, Volume and Issue: unknown, P. 100570 - 100570

Published: Nov. 1, 2024

Language: Английский

Citations

0
The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes DOI Creative Commons
Johannes Heidenberger,

Raphael Hangel,

Eva I. Reihs

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 10, 2024

Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing overall chronic nature of desmopathy. A major challenge has been lack representative two-dimensional (2D) vitro models mimicking processes presence dynamic mechanical strain, both being crucial for homeostasis. Physiological levels strain exert anti-inflammatory effects, while excessive can facilitate mechanisms. Adhering 3Rs (Replacement, Reduction Refinement) principles animal research, this study aims investigate role a biomechanical environment on mechanisms by combining Flexcell culture system with primary human ligamentocytes pathology. Primary from OA patients were cultured under animal-free conditions platelet lysate, exposed either IL-1β or TGF-β3 simulate different microenvironments. Cells subjected magnitudes strain. Results showed that cells aligned along force axis This highlights critical microenvironment modulating cellular responses ligamentocyte pathology, providing valuable insights into complex interplay between stimuli cytokine signaling. These findings not only advance our understanding biology but also pave way development more targeted therapeutic strategies injuries diseases, potentially improving patient outcomes orthopedic medicine.

Language: Английский

Citations

0