Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy DOI

Xue‐Na Li,

Ya‐Ping Lin, Meng‐Meng Han

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given inherent mechanosensitivity of fibrotic lungs, where type II epithelial cells (AEC IIs) are subjected persistent stretching overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative develop effective strategies modulate microenvironment. Herein, cyclo (RGDfC) peptide-decorated zeolitic imidazolate framework-8 nanoparticles (named ZDFPR NPs) constructed target repair aberrant force levels in pathological lungs. Specifically, reduces tension AEC IIs pH-responsive NPs release zinc ions 7, 8-dihydroxyflavone promote differentiation. Meanwhile, between myofibroblast contractility extracellular matrix stiffness mechanotransduction disrupted fasudil inhibition ROCK signaling pathway. The results show successfully restored homeostasis terminated process bleomycin-induced mice. This study not only presents a promising strategy for modulating but also pioneers novel avenue IPF treatment.

Language: Английский

Mechanisms of assembly and remodelling of the extracellular matrix DOI
Alexandra Naba

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Language: Английский

Citations

42
Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects DOI Creative Commons
Zhipeng Cao,

Sadia Quazi,

Sakshi Arora

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 9, 2025

Abstract Research into cancer treatment has been mainly focused on developing therapies to directly target cells. Over the past decade, extensive studies have revealed critical roles of tumour microenvironment (TME) in initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) emerged as one primary contributors shaping TME, creating a favourable environment for development. Many preclinical identified promising targets CAFs, demonstrating remarkable efficacy some CAF-targeted treatments models. Encouraged by these compelling findings, therapeutic strategies now advanced clinical evaluation. We aim provide comprehensive review relevant subjects including CAF-related markers targets, their multifaceted roles, current landscape ongoing trials. This knowledge can guide future research CAFs advocate investigations targeting CAFs.

Language: Английский

Citations

8
Inhalable siRNA Targeting IL-11 Nanoparticles Significantly Inhibit Bleomycin-Induced Pulmonary Fibrosis DOI

Shengting Dong,

Huapan Fang, Junjie Zhu

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

For idiopathic pulmonary fibrosis (IPF), interleukin 11 (IL-11) is a pivotal cytokine that stimulates the transformation of fibroblasts into myofibroblasts, thus accelerating progression fibrosis. Here, we develop an innovative inhalable small interfering RNA (siRNA) delivery system termed PEI-GBZA, which demonstrates impressive efficiency in loading siIL-11 targeting IL-11 (siIL-11) and substantially suppresses differentiation myofibroblasts epithelial-mesenchymal transition (EMT), reduces neutrophil macrophage recruitment, ultimately relieves established fibrotic lesions IPF model. PEI-GBZA prepared by modifying low-molecular-weight polyethylenimine (PEI) with 4-guanidinobenzoic acid (GBZA). The resulting may effectively encapsulate through variety interactions such as hydrophobic, hydrogen bonding, electrostatic interactions, creating stable carrier/siIL-11 nanoparticles (PEI-GBZA/siIL-11 NPs). Upon inhalation, PEI-GBZA/siIL-11 NPs demonstrate effective retention lesions, leading to marked mitigation disease bleomycin-induced Impressively, this inhalation therapy exhibits negligible systemic toxicity. This work provides universal noninvasive therapeutic platform holds significant promise for respiratory diseases. potential clinical application substantial, offering frontier treatment potentially other disorders.

Language: Английский

Citations

5
pH-Responsive Hydrogel with Dual-crosslinked Network of Polyvinyl Alcohol/Boric Acid for Controlled Release of Salvianolic Acid B: Novel Pro-Regenerative Mechanisms in Scar Inhibition and Wound Healing DOI Creative Commons
Wei Song, Chao Zhang, Li Zhao

et al.

Regenerative Biomaterials, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 1, 2025

Abstract This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol (PVA) and boric acid (BA) designed for the controlled release salvianolic B (SAB), addressing critical challenge scar formation skin regeneration. The dual-crosslinked network architecture exhibits remarkable pH sensitivity, enabling it to achieve peak SAB within 48 hours in acidic microenvironment characteristic early-stage wound healing. In vitro assessments demonstrated that PVA-BA-SAB significantly inhibits fibroblast activation mitigates abnormal collagen deposition, effectively preventing excessive formation. Transcriptome sequencing reveals potential role balancing TGF-β Wnt signaling pathways. Furthermore, vivo studies revealed enhanced tissue regeneration, characterized by improved organization increased vascularization, as well promotion mature hair follicle development. hydrogel’s biocompatibility, mechanical robustness adhesive properties were also thoroughly evaluated, confirming its suitability clinical applications. These findings suggest fully exerts excellent characteristics biomaterials maximizes pharmacological effect SAB. Our innovative drug delivery system not only facilitates healing but offers strategic approach minimize scarring. research provides valuable insights into therapeutic strategies effective management repair.

Language: Английский

Citations

2
IFN-γ-mediated inhibition of JAK/STAT signaling via nano-scutellarin treatment is an efficient strategy for ameliorating liver fibrosis DOI Creative Commons
Qin Sun,

Bangguo Liu,

Juan Huang

et al.

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

Published: Feb. 17, 2025

Language: Английский

Citations

2
Cancer associated fibroblasts in cancer development and therapy DOI Creative Commons

Hongyuan Jia,

Xingmin Chen,

Linling Zhang

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 28, 2025

Cancer-associated fibroblasts (CAFs) are key players in cancer development and therapy, they exhibit multifaceted roles the tumor microenvironment (TME). From their diverse cellular origins, CAFs undergo phenotypic functional transformation upon interacting with cells presence can adversely influence treatment outcomes severity of cancer. Emerging evidence from single-cell RNA sequencing (scRNA-seq) studies have highlighted heterogeneity plasticity CAFs, subtypes identifiable through distinct gene expression profiles properties. multiple mechanisms, including regulation extracellular matrix (ECM) remodeling, direct promotion growth provision metabolic support, promoting epithelial-mesenchymal transition (EMT) to enhance invasiveness growth, as well stimulating stem cell properties within tumor. Moreover, induce an immunosuppressive TME contribute therapeutic resistance. In this review, we summarize fundamental knowledge recent advances regarding focusing on sophisticated potential targets. We discuss various strategies target ECM modulation, elimination, interruption CAF-TME crosstalk, CAF normalization, approaches developing more effective treatments. An improved understanding complex interplay between is crucial for new targeted therapies

Language: Английский

Citations

2
Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori DOI Creative Commons
Nianshuang Li, Sihai Chen, Xinbo Xu

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Helicobacter pylori (H. pylori) infection is the main risk for gastric cancer (GC). However, cellular heterogeneity and underlying molecular mechanisms in H. pylori-driven tumorigenesis are poorly understood.

Language: Английский

Citations

12
Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin–mediated engagement of Piezo1 DOI Creative Commons
Maya Ezzo,

Klaus‐Dieter Spindler,

J. Wang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(43)

Published: Oct. 23, 2024

Fibrosis—excessive scarring after injury—causes >40% of disease-related deaths worldwide. In this misguided repair process, activated fibroblasts drive the destruction organ architecture by accumulating and contracting extracellular matrix. The resulting stiff scar tissue, in turn, enhances fibroblast contraction—bearing question how positive feedback loop begins. We show that direct contact with profibrotic but not proinflammatory macrophages triggers acute contractions. contractile response depends on αvβ3 integrin expression Piezo1 fibroblasts. touch elevates cytosolic calcium within seconds, followed translocation transcription cofactors nuclear factor T cells 1 Yes-associated protein, which activation hours. Intriguingly, induce mechanical stress soft matrix alone suppresses their spontaneous activation. propose suitable mechanically kick-starts an otherwise nonpermissive environment. molecular components mediating macrophage-fibroblast mechanotransduction are potential targets for antifibrosis strategies.

Language: Английский

Citations

10
Biomimetic Topological Micropattern Arrays Regulate the Heterogeneity of Cellular Fates in Lung Fibroblasts between Fibrosis and Invasion DOI
Xinglong Zhu, Shengqiang Mao, Ying Yang

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: 19(1), P. 580 - 599

Published: Jan. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is characterized by persistent tissue injury, dysregulated wound healing, and extracellular matrix (ECM) deposition myofibroblasts (MFs) through the fibroblast-to-myofibroblast transition (FMT). Implicit in FMT process are changes ECM cellular topology, but their relationship with lung fibroblast phenotype has not been explored. We engineered topological mimetics of alignment cues (anisotropy/isotropy) using decellularized micropattern arrays investigated effects topology on fates MRC-5 fibroblasts. found that isotropic cells presented cytoskeleton, increased cell–cell adhesions a multicellular architecture overlap, actin–myosin development, enhanced focal adhesion cell junction random alignment. Besides, anisotropic fibroblasts were activated into regular an remodeling profile. In contrast, developed highly invasive expressing molecules, including CD274/programmed death-ligand 1 (PD-L1), communication network factor 2 (CCN2)/connective growth (CTGF), hyaluronan synthase (HAS2), semaphorin 7A (SEMA7A), downregulated genes. Moreover, also showed higher expressions Ki-67 cyclin D1 (CCND1), resistance to apoptosis/senescence, decreased autophagy. The regulated heterogeneity resulted positive feedback between structure, which may aggravate lead priming malignant microenvironment during carcinogenesis. Using versatile platform array, we can only visualize interaction mechanism select potential clinical targets for diagnosis therapeutics.

Language: Английский

Citations

1
Electroactive Asymmetric Dressing for Spatiotemporal Deep Burn Scarless Healing and Management DOI Open Access
Hanbai Wu, Xiong Zhou, Chuanwei Zhi

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Burn care and treatment differ markedly from other types of wounds, as they are significantly more prone to infections struggle maintain fluid balance post-burn. Moreover, the limited self-healing abilities exacerbate likelihood scar formation, further complicating recovery process. To tackle these issues, an asymmetric wound dressing comprising a quercetin-loaded poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB@Qu) hydrophilic layer zinc oxide nanoparticle-loaded, thermally treated polyvinylidene fluoride (HPVDF@ZnO) hydrophobic is designed. This provided antibacterial property exudate management in early stages burn treatment, preventing infection maintaining moisture at site. As healing progresses, electroactive properties HPVDF@ZnO quercetin P34HB@Qu synergistically regulate cell migration differentiation, accelerating facilitating scar-free regeneration. Furthermore, assisted regeneration skin appendages. study underscores full-cycle strategy versatile dressings for spatiotemporal injury scarless healing.

Language: Английский

Citations

1