YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Oct. 20, 2023

Maladaptive repair of acute kidney injury (AKI) is associated with a high risk developing chronic disease deemed irremediable even in present days. When AKI arises from ischemia-reperfusion injury, hypoxia usually plays major role. Although both hypoxia-inducible factor-1α (HIF-1α) and yes-associated protein (YAP) have been proven to promote renal cell survival under hypoxia, there lack research that studies the crosstalk two its effect on repair. In studying crosstalk, CoCl2 was used create mimetic hypoxic environment. Immunoprecipitation proximity ligation assays were performed verify interactions. The results show HIF-1α interacts YAP promotes nuclear translocation at density conditions, suggesting serves as direct carrier enables translocation. This first study identify crucial pathway for conditions. Once translocated into nucleus, protects cells DNA damage apoptosis Since it unlikely translocate nucleus without HIF-1α, any treatment fosters between holds potential improve recovery insults.

Language: Английский

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Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis

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

Published: Aug. 21, 2024

Abstract Addressing osteoporosis‐related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment patients with iron‐overloaded osteoporosis, modified implant surface possesses multiple endogenous modulation capabilities. After implantation, brush‐like initially resist macrophage adhesion, thereby reducing level of immune inflammation. Over time, molecular chains undergo conformational changes due to Fe (III) mediated self‐assembly, transforming into mechanistic signals. These signals are then specifically transmitted pre‐osteoblast cell through binding capacity KRSR short peptide at terminus, induced their osteogenic differentiation YAP/β‐catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds macromolecular side groups, resulting release alendronate (ALN). This process further improves local osteoporotic microenvironment. modification tailors repair individual conditions, automatically realize regulation once implanted, and truly spontaneous activation series responses conducive vivo. It evidenced by improved regeneration rabbits supported vitro validations.

Language: Английский

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Tunable Integrin–Ligand Coupling Strength Modulates Cellular Adaptive Mechanosensing

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

Published: March 7, 2025

Cells sense and respond to the matrix by exerting traction force through binding of integrins an integrin-specific ligand. Here, Arg-Gly-Asp (RGD) peptide is covalently conjugated double-stranded DNA (dsDNA) stem-loop (slDNA) tethers with a tension tolerance 43pN immobilized on PEG substrate. Unlike dsDNA, which ruptured under high tension, leading removal RGD, slDNA remains bound even when ruptured. Our results suggest that cells adapt their adhesion state modulating actin filament polymerization cofilin phosphorylation, effectively balancing talin conformation prevent dsDNA rupture maintain normal adhesion. This phenomenon, termed integrin-ligand coupling strength, mediated cellular adaptive mechanosensing. Furthermore, we demonstrate positive durotaxis can shift negative durotaxis, depending strength. study highlights significance strength in cell-extracellular (ECM) interactions offers new insights into designing biomaterials tunable adhesive properties for cell-based applications.

Language: Английский

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Research Progress of Mesenchymal Stem Cell Engineering Modification Strategies in Stem Cell-Based Therapy

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(01), P. 2286 - 2296

Published: Jan. 1, 2025

Language: Английский

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Inhibiting mechanotransduction prevents scarring and yields regeneration in a large animal model

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(786)

Published: Feb. 19, 2025

Modulating mechanotransduction by inhibiting yes-associated protein (YAP) in mice yields wound regeneration without scarring. However, rodents are loose-skinned and fail to recapitulate key aspects of human repair. We sought elucidate the effects YAP inhibition red Duroc pig wounds, most human-like model show that one-time treatment with verteporfin, a inhibitor, immediately after wounding is sufficient prevent scarring drive pigs. By performing single-cell RNA sequencing (scRNA-seq) on porcine wounds conjunction spatial proteomic analysis, we found perturbations fibroblast dynamics verteporfin presence putative pro-regenerative/profibrotic fibroblasts enriched regenerating/scarring respectively. also identified differences myeloid cell subpopulations linked this observation increased elaboration interleukin-33 (IL-33) regenerating wounds. Finally, validated our findings xenograft containing neonatal foreskin engrafted onto nude used scRNA-seq cells draw parallels subpopulation Collectively, provide support for clinical translation local inhibitors skin scarring, they clarify YAP/IL-33 signaling axis large animal regeneration.

Language: Английский

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