Exploring Piezo1, Piezo2, and TMEM150C in Human Brain Tissues and Their Correlation with Brain Biomechanical Characteristics DOI Creative Commons
Arjun Raha, Yuning Wu, Lily Zhong

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet underlying mechanistic model of signaling pathways in mechanotransduction remains enigmatic. To bridge this gap, we introduced an situ multi-scale platform, through which delineate comprehensive biomechanical traits white matter (WM), gray-white junctions (GW junction), pons across human tissue from four distinct donors. We investigate three-dimensional expression patterns Piezo1, Piezo2, TMEM150C, while also examining their associated histological features networks, particularly focusing on YAP/β-catenin axis. Our results showed that characteristics (including stiffness, spring term, equilibrium stress) with Piezo1 vary depending specific region. Moving beyond our result demonstrated significant positive correlations Piezo2 stiffness WM. Meanwhile, TMEM150C was shown to be correlated viscoelastic properties Given heterogeneity nature tissue, investigated TMEM150C. suggested three mechanosensitive proteins remained consistent different vertical planes within sections. findings not only establish as mechanosensors regulate region-specific activities, but unveil paradigm connecting activities variations individuals.

Language: Английский

Phosphorylation of KRT8 (keratin 8) by excessive mechanical load-activated PKN (protein kinase N) impairs autophagosome initiation and contributes to disc degeneration DOI
Di Wang, Qiliang Shang,

Jianxin Mao

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 19(9), P. 2485 - 2503

Published: March 10, 2023

Excessive mechanical load (overloading) is a well-documented pathogenetic factor for many mechano stress-induced pathologies, i.e. intervertebral disc degeneration (IDD). Under overloading, the balance between anabolism and catabolism within nucleus pulposus (NP) cells are badly thrown off, NP undergo apoptosis. However, little known about how overloading transduced to contributes degeneration. The current study shows that conditional knockout of Krt8 (keratin 8) aggravates load-induced IDD in vivo, overexpression endows greater resistance overloading-induced apoptosis vitro. Discovery-driven experiments phosphorylation KRT8 on Ser43 by activated RHOA-PKN (protein kinase N) impedes trafficking Golgi resident small GTPase RAB33B, suppresses autophagosome initiation IDD. Overexpression knockdown Pkn1 Pkn2, at an early stage IDD, ameliorates degeneration; yet only when treated late therapeutic effect. This validates protective role during demonstrates targeting activation PKNs could be novel effective approach pathologies with wider window opportunity.

Language: Английский

Citations

24
The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation DOI Open Access
Fumihiko Nakamura

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2135 - 2135

Published: Feb. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Language: Английский

Citations

8
Nanoscale surface coatings and topographies for neural interfaces DOI Creative Commons
Younghak Cho, Yunyoung Choi, Hyejeong Seong

et al.

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 175, P. 55 - 75

Published: Dec. 22, 2023

With the lack of minimally invasive tools for probing neuronal systems across spatiotemporal scales, understanding working mechanism nervous system and limited assessments available are imperative to prevent or treat neurological disorders. In particular, nanoengineered neural interfaces can provide a solution this technological barrier. This review covers recent surface engineering approaches, including nanoscale coatings, range topographies from microscale nanoscale, primarily focusing on neural-interfaced biosystems. Specifically, immobilization bioactive molecules fertilize cell lineage, topographical induce mechanotransduction in cells, enhanced cell-chip coupling using three-dimensional structured surfaces highlighted. Advances interface design will help us understand system, thereby achieving effective treatments disorders.\ • focuses designing with chemical modification at multiscale perspective. Versatile coatings summarized. Recent advances materials applicable culture, electrophysiological sensing, implants reviewed.

Language: Английский

Citations

13
The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme DOI
Yafei Wang, Ying Yu, Jiahua Yu

et al.

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Jan. 22, 2025

Language: Английский

Citations

0
Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction DOI Creative Commons
Kazuo Katoh

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 166 - 166

Published: Jan. 23, 2025

Mechano-signal transduction is a process in which cells perceive extracellular mechanical signals, convert them into intracellular biochemical and produce response. Integrins are cell surface receptors that sense the cues bind to matrix (ECM). This binding induces integrin clustering activation. Cytoplasmic tails of activated integrins interact induce cytoskeleton tensions via several adaptor proteins. monitor stiffness modulate ECM downstream signaling pathways regulating expression genes components. Integrin-mediated mechano-transduction very crucial for as it regulates physiology both normal diseased conditions according cues. It proliferation, survival, migration. Abnormal such extreme prolonged stress result pathological including fibrosis, cancers, skin, autoimmune disorders. paper aims explore role their associated proteins mechano-signal transduction. highlights targets therapy development. Furthermore, also presents challenges targeted drug development, can be resistance cytotoxicity. concluded this research on integrin-mediated its relationship with pathologies will an important step towards development effective therapies.

Language: Английский

Citations

0
Immediate Changes in the Elasticity of Tissue and the Pain Pressure Threshold in Cesarean Scar Tissue After a Vacuum Intervention: An Open Clinical Trial DOI Creative Commons
Ana González-Muñoz, Santiago Navarro‐Ledesma

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 557 - 557

Published: Feb. 21, 2025

Background/Objectives: Cesarean section (C-section) scars are commonly linked to reduced tissue elasticity and increased pain due adhesion formation. Addressing these concerns is essential improving patient comfort functional outcomes. This study aimed assess the immediate effects of vacuum therapy on skin sensitivity in C-section scar tissue. Methods: Thirty-one women with older than six months less two years participated an open clinical trial. The was assessed using Adheremeter, measured through Pressure Pain Threshold (PPT) algometry. intervention consisted a 15 min session AeroFlow® device that targeted surrounding areas. Results: resulted significant improvements at multiple assessment points, particularly regions fascial restrictions (p < 0.05). Concurrently, PPT values decreased, indicating reduction around area These findings suggest may enhance flexibility alleviate adherent scars. Conclusions: demonstrated potential as effective improve reduce Adheremeter-based provided valuable insights into biomechanical properties supported its use management protocols. approach offers promising, non-invasive strategy for personalized treatment, ultimately aiming outcomes quality life.

Language: Английский

Citations

0
Mechanosensitive apoptosis in Alzheimer’s disease DOI Open Access

G.V. Sapozhnikov,

Rajesh Ranganathan, Shoutang Wang

et al.

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: 5(2)

Published: April 28, 2025

The incidence of neurodegenerative diseases is increasing exponentially, with Alzheimer’s disease (AD) being a notorious example. AD progressive, aging-related, multifactorial disease, and no uniform theory exists regarding its etiology. One hypothesis implicates defects in the organism’s mechanosensing mechanotransduction mechanisms. deleterious effects mechanical stress neurodegeneration have been proven through multiple studies observations, but pathways linking inputs to progression remain unclear. It has proposed that nervous tissue primarily responds sources astrocytes microglia, activation Piezo1 TRPV4 ion channels. An area current research examining might be involved elevated oxidative dysregulated apoptotic pathways. We summarized understanding related AD. Our review indicated relationship between crucial Hippo pathway (MST1 humans) KCNN4 worth following up future studies. noted G3BP1 G3BP2 FlnA-mediated are linked ceramide production, along their interaction granules - key element for onset apoptosis, which assembled, among others, response stress. This sheds light on how input disrupts what implications also identifies potential targets focus.

Language: Английский

Citations

0
Engineered cell culture microenvironments for mechanobiology studies of brain neural cells DOI Creative Commons

Lucía Castillo Ransanz,

Pieter F. J. van Altena, Vivi M. Heine

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Dec. 14, 2022

The biomechanical properties of the brain microenvironment, which is composed different neural cell types, extracellular matrix, and blood vessels, are critical for normal development functioning. Stiffness, viscoelasticity spatial organization tissue modulate proliferation, migration, differentiation, function. However, mechanical aspects microenvironment largely ignored in current culture systems. Considering high promises human induced pluripotent stem cell- (iPSC-) based models disease modelling new treatment development, light physiological relevance neuromechanobiological features, applications

Language: Английский

Citations

16
Micro- and Nanostructured Fibrous Composites via Electro-Fluid Dynamics: Design and Applications for Brain DOI Creative Commons
Nergis Zeynep Renkler, Stefania Scialla, Teresa Russo

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(1), P. 134 - 134

Published: Jan. 19, 2024

The brain consists of an interconnected network neurons tightly packed in the extracellular matrix (ECM) to form complex and heterogeneous composite tissue. According recent biomimicry approaches that consider biological features as active components biomaterials, designing a highly reproducible microenvironment for cells can represent key tool tissue repair regeneration. Indeed, this is crucial support cell growth, mitigate inflammation phenomena provide adequate structural properties needed damaged tissue, corroborating activity vascular ultimately functionality neurons. In context, electro-fluid dynamic techniques (EFDTs), i.e., electrospinning, electrospraying related techniques, offer opportunity engineer wide variety substrates by integrating fibers, particles, hydrogels at different scales—from several hundred microns down tens nanometers—for generation countless patterns physical biochemical cues suitable influencing vitro response coexistent populations mediated surrounding microenvironment. review, overview technological approaches—based on EFDTs—for engineering fibrous and/or particle-loaded will be proposed. second section review primarily focus describing current future use composites applications, ranging from therapeutic diagnostic/theranostic regeneration, with ultimate goal providing insightful information guide research efforts toward development more efficient reliable solutions.

Language: Английский

Citations

2
Substrate stiffness-dependent activation of Hippo pathway in cancer associated fibroblasts DOI
Gerard Rubí-Sans, Agata Nyga, Miguel A. Mateos‐Timoneda

et al.

Biomaterials Advances, Journal Year: 2024, Volume and Issue: 166, P. 214061 - 214061

Published: Oct. 9, 2024

Language: Английский

Citations

2