RAS signaling pathway is essential in regulating PIEZO1‐mediated hepatic iron overload in dehydrated hereditary stomatocytosis DOI Creative Commons
Barbara Eleni Rosato,

Vanessa D’Onofrio,

Roberta Marra

et al.

American Journal of Hematology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract PIEZO1 encodes a mechanoreceptor, cation channel activated by mechanical stimuli. Gain‐of‐function (GoF) variants in cause dehydrated hereditary stomatocytosis (DHS), or xerocytosis, pleiotropic syndrome characterized anemia and iron overload. DHS patients develop hepatic overload independent of the degree transfusion regimen. PIEZO1‐GoF suppress hepcidin expression both cellular model constitutive/macrophage‐specific Piezo1‐GoF mice model. Therefore, regulate crosstalk between hepatocytes (HCs) macrophages with still unknown mechanism. Transcriptomic proteomics analysis human Hep3B cells engineered for PIEZO1‐R2456H variant (PIEZO1‐KI) revealed alterations actin cytoskeleton regulation, MAPK cascade, RAS signaling. These changes mainly occur through novel key regulator, RRAS, whose protein mRNA levels are regulated activation inhibition. This regulation was further confirmed C57BL/6 mouse primary HCs treated Yoda‐1 and/or GsMTx‐4. Indeed, PIEZO1‐KI exhibited hyper‐activated RAS‐GTPase activity that is rescued inhibition, restoring gene HAMP . A negative correlation signaling inhibiting MEK1‐2 activity. Conversely, requires downregulation confirming feedback RAS‐MAPK BMP/SMADs pathways regulation. We demonstrated influence organization activating system. Understanding role regulating metabolism could pave way new therapeutic strategies other conditions

Language: Английский

Piezo1 promotes vibration-induced vascular smooth muscle injury by regulating the NF-κB/p65 axis DOI Creative Commons
Yingshan Zeng,

Zhi-Quan Wu,

Mingmei Xiong

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 21, 2025

Vibration induced damage to the peripheral circulatory system is thought be an early stage of hand-arm vibration syndrome (HAVS) caused by occupational exposure hand-transmitted (HTV). This study investigated mechanisms underlying vibration-induced vascular injury, focusing on role Piezo1, a mechanosensitive channel, and its association with NF-κB/p65 signaling pathway. We demonstrated that leads Piezo1-mediated upregulation angiogenic chemokines, including CCL2, CCL5, CXCL1, CXCL2, CXCL10, through To mimic effects vibration, rat model cellular were used. Animal models showed dysfunction while increasing Piezo1 expression. knockdown or p65 inhibition attenuated these effects, suggesting crucial for Piezo1-NF-κB/p65 axis in dysfunction. Furthermore, chemokines identified as potential biomarkers diagnosis HAVS occupationally exposed individuals. These results highlight pathway therapeutic targets underscore need further validation human samples exploration additional involved injury. triggers via pathway, leading syndrome.

Language: Английский

Citations

1
GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3 DOI Creative Commons
Xiaobo Wang,

Bingyu Wang,

Jiawei Shi

et al.

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 1174 - 1186

Published: Jan. 13, 2025

This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator this process. A ferroptosis-related gene risk coefficient model was constructed using differential expression analysis GSE70362 dataset. The significant factor IVDD progression. shown to promote nucleus pulposus cells (NPCs) by regulating AKR1C3 through TLR2 pathway. In vitro vivo experiments demonstrated that knockdown reduced ferroptosis, improved cell viability, mitigated extracellular matrix degradation, whereas overexpression exacerbated these processes. Furthermore, found be crucial for GATA6-mediated modulation TLR2-AKR1C3 axis significantly impacted NPCs. These findings suggest targeting its downstream pathway may provide new therapeutic approaches IVDD.

Language: Английский

Citations

1
Electroacupuncture regulates SIRT1/p53/p21 signaling pathway to prevent stress-induced premature senescence of nucleus pulposus cells in degenerative intervertebral discs DOI
Min Wang, Jiabao Huang, Jing Zou

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114114 - 114114

Published: Jan. 31, 2025

Language: Английский

Citations

1
Targeting Piezo1 channel to alleviate intervertebral disc degeneration DOI Creative Commons

Feiyun Li,

Mingjue Chen, Mengrui Zhang

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 145 - 158

Published: March 1, 2025

Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in pathology and potential treatment To investigate effects disc-specific Piezo1 deletion, we generated Aggrecan CreERT2 ; fl/fl mice examined both lumbar spine instability (LSI)- aging-induced Additionally, effect pharmacological inhibition was evaluated using GsMTx4, potent antagonist, an ex vivo model stimulated with IL-1β induce Assessments included histological examinations, immunofluorescence, western blot analyses thoroughly characterize alterations discs. Elevated expression detected nucleus pulposus (NP) discs advanced degeneration aged human patients. Inducible deletion aggrecan-expressing cells significantly reduced degeneration, decreased extracellular matrix (ECM) degradation, lowered apoptosis NP cells, observed those undergoing LSI surgery. Excessive compression loading (CL) upregulated expression, induced ECM disruption, increased whereas GsMTx4 effectively mitigated these pathological changes. Furthermore, cultured mouse discs, alleviated IL-1β-induced degenerative damages, restored anabolism, apoptosis. The findings suggest that plays critical development highlight its as therapeutic target. Inhibiting could offer novel strategy for treating or preventing this disease. research highlights involvement emphasizes targeting delay reverse condition.

Language: Английский

Citations

1
The emerging role of Piezo1 in the musculoskeletal system and disease DOI Creative Commons
Lei Lei,

Zhenkang Wen,

Mingde Cao

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(10), P. 3963 - 3983

Published: Jan. 1, 2024

Piezo1, a mechanosensitive ion channel, has emerged as key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such lymphatic vessel development, axon growth, vascular immunoregulation, blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, homeostasis, recently attracted attention regarding the significance of Piezo1. This review aims to provide comprehensive summary current research on Piezo1 highlighting its impact bone formation, myogenesis, chondrogenesis, intervertebral disc tendon matrix cross-linking, physical activity. Additionally, we explore potential targeting therapeutic approach disorders, including osteoporosis, muscle atrophy, degeneration, osteoarthritis.

Language: Английский

Citations

5
Chewing-Activated TRPV4/PIEZO1–HIF-1α–Zn Axes in a Rat Periodontal Complex DOI Creative Commons
Yongmei Wang, Brandon H. Lee, Zhan‐Qing Yang

et al.

Journal of Dental Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

The upstream mechanobiological pathways that regulate the downstream mineralization rates in periodontal tissues are limitedly understood. Herein, we spatially colocalized and correlated compression tension strain profiles with expressions of mechanosensory ion channels (MS-ion) TRPV4 PIEZO1, biometal zinc, mitochondrial function marker ( MFN2), cell senescence indicator p16), oxygen status hypoxia-inducible factor-1α HIF-1α) rats fed hard soft foods. observed zinc related cellular homeostasis vivo were ascertained by PIEZO1 agonists antagonists on human ligament fibroblasts ex vivo. Four-week-old male Sprague-Dawley n = 3) or foods for 4 wk (in vivo). Significant changes alveolar socket root shapes decreased space increased cementum volume fraction maxillae reduced loads (soft food). Reduced impaired distally localized compression-stimulated mesially tension-stimulated TRPV4, mesial distal regions. switch HIF-1α from food–distal to food–mesial indicated a plausible effect shear-regulated blood flows complex. Blunting activating MS-ion channel-specific fibroblast cultures vitro) positive correlation between levels transporters but not channel expressions. effects chewing analogous vitro. Study results collectively illustrated tension-induced compression-induced activations necessary metabolism. An hypoxic state functional can be conducive environment growth. From practical standpoint, dose rate–controlled modulate compression-specific activation, transcription. These mechanobiochemical events indicate catalytic role mineralization, maintenance, dentoalveolar joint function.

Language: Английский

Citations

0
The landscape of cell lineage tracing DOI
Feng Ye, Liu Guang, Haiqing Li

et al.

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

Citations

0
Dysregulation of Calcium Homeostasis: An Important Factor Leading to Ferroptosis in Cardiovascular Diseases DOI Open Access
Yifan Zhang,

Lei-Yin Zheng,

Tongtong Che

et al.

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Cardiovascular disease is a circulatory system involving the heart and blood vessels, which one of main causes human health loss even life-threatening. Ca2+ an important signal molecule. Free calcium ions in cytoplasm are involved various physiological biochemical reactions cells. Ferroptosis programmed cell death driven by lipid peroxidation dependent on free ferrous ions. The essence ferroptosis accumulation peroxide caused increase intracellular ion content, leads to damage phospholipid membrane eventually death. Studies have shown that homeostasis occurrence development cardiovascular diseases, but relationship between them remains be clarified. This article reviews pathways regulating cells mechanism ferroptosis, discusses two expected provide novel strategies for alleviating treating diseases.

Language: Английский

Citations

0
Inhibition of TrkB-BDNF positive feedback loop attenuates intervertebral disc degeneration and low back pain in a composite mouse model DOI
Xiang Ao, Kun Li, Yujie Chen

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Cell compression – relevance, mechanotransduction mechanisms and tools DOI
Laura M. Faure, Valeria Venturini, Pere Roca‐Cusachs

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(6)

Published: March 15, 2025

ABSTRACT From border cell migration during Drosophila embryogenesis to solid stresses inside tumors, cells are often compressed physiological and pathological processes, triggering major responses. Cell compression can be observed in vivo but also controlled vitro through tools such as micro-channels or planar confinement assays. Such have recently become commercially available, allowing a broad research community tackle the role of variety contexts. This has led discovery conserved compression-triggered modes, fate determinants mechanosensitive pathways, among others. In this Review, we will first address different ways which their biological Then, discuss distinct mechanosensing mechanotransducing pathways that activate response compression. Finally, describe systems been engineered compress cells.

Language: Английский

Citations

0