Extracellular vimentin amplifies inflammation: Perspectives for immune injury and therapeutics for periodontitis

The FASEB Journal, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 6, 2025

Periodontitis is an inflammatory disease triggered by microbial biofilms that promote immune dysfunction and tissue destruction of tooth-supporting tissues. The search for soluble mediators amplify responses matrix degradation in periodontal tissues has implicated extracellular vimentin (ECV) as a signaling ligand damage-associated molecular pattern the pathogenesis periodontitis. Intracellular filaments are essential structural integrity cells preservation homeostasis. These important determinants health periodontium many other organs. But inflamed tissues, intracellular disassembled. Vimentin subsequently released from into space form where it drives destruction. We discuss role ECV molecule several apply these data to understand how diseases like periodontitis, amplifies contribute progression. Arising data, we consider novel therapeutic opportunities limiting targeting treatment disorders

Язык: Английский

---

Maimendong decoction modulates the PINK1/Parkin signaling pathway alleviates type 2 alveolar epithelial cells senescence and enhances mitochondrial autophagy to offer potential therapeutic effects for idiopathic pulmonary fibrosis

Journal of Ethnopharmacology, Год журнала: 2025, Номер 345, С. 119568 - 119568

Опубликована: Март 2, 2025

Язык: Английский

---

An Update on Molecular Mechanisms of Scarring—A Narrative Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(21), С. 11579 - 11579

Опубликована: Окт. 28, 2024

Fibroblasts, the principal cellular mediators of connective tissue remodeling, play a crucial role in formation physiological and pathological scars. Understanding intricate interplay between fibroblasts other molecular components is essential for elucidating underlying mechanisms driving scar formation. Hypertrophic scars, keloids atrophic scars arise from dysregulated wound healing processes characterized by persistent inflammation, aberrant collagen deposition, impaired extracellular matrix remodeling. Fibroblasts central pathogenesis such subsequently contributing to raised or depressed fibrotic lesions. The investigation complex interactions microenvironment developing targeted therapeutic interventions aimed at modulating fibroblast activity improving clinical outcomes patients with Further research into pathways governing behavior their heterogeneity holds promise advancing management strategies. This narrative review was performed shed light on behind formation, special focus different types providing insights pathophysiology these conditions. Through analysis current knowledge, this seeks identify key involved activation, synthesis, remodeling hypertrophic scar, keloid,

Язык: Английский

---

Vimentin promotes collective cell migration through collagen networks via increased matrix remodeling and spheroid fluidity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 17, 2024

The intermediate filament (IF) protein vimentin is associated with many diseases phenotypes of enhanced cellular migration and aggressive invasion through the extracellular matrix (ECM) tissues, but vimentin's role in in-vivo cell still largely unclear. Vimentin important for proper adhesion force generation, which are critical to migration; yet cytoskeleton also hinders ability cells squeeze small pores ECM, resisting migration. To identify collective migration, we generate spheroids wide-type vimentin-null mouse embryonic fibroblasts (mEFs) embed them a 3D collagen matrix. We find that loss significantly impairs spheroid collectively expand networks remodel network. Traction analysis reveals null exert less contractile than their wild-type counterparts. In addition, made mEFs only unit length filaments (ULFs) exhibit similar behavior as spheroids, suggesting filamentous required promote vimentin-mediated expansion dependent on metalloproteinase (MMP) degradation Further, vertex model simulation embedded ECM indicates behave more fluid-like, enabling active pulling reconstructing surrounding Altogether, these results signify VIF plays enhancing migratory persistence environments MMP transportation tissue fluidity.

Язык: Английский

---

Zinc Deficiency Causes Glomerulosclerosis and Renal Interstitial Fibrosis Through Oxidative Stress and Increased Lactate Metabolism in Rats

Biological Trace Element Research, Год журнала: 2024, Номер unknown

Опубликована: Июль 19, 2024

Abstract Chronic kidney disease (CKD) is a highly prevalent condition characterized by renal fibrosis as its ultimate manifestation. Zinc deficiency closely associated with CKD, evidenced link to fibrosis. Recently, local lactic acidosis has been demonstrated promote Under zinc-deficient conditions, mitochondrial function compromised and abnormal lactate metabolism might be induced potentially. However, it remains unclear whether zinc leads through acidosis. rat models were successfully established feeding diet. Western blot, qPCR, IHC, other experiments employed investigate the key markers molecular mechanisms of glomerulosclerosis interstitial Our results indicate that reduces specific podocytes (podocalyxin, WT1, nephrin) activates Wnt3a/β-catenin pathway, pathway in podocyte injury. Concurrently, indicated increased urinary microalbumin serum creatinine levels along histological alteration observed PAS Masson staining rats. Furthermore, various degrees upregulation for several including α-SMA, FN1 collagen III are also revealed. These findings further confirmed IHC. Additionally, alterations four EMT process, N-cadherin, E-cadherin, Vimentin, snail, consistent expectations. We then activation non-canonical TGF-β1 known PI3K/AKT/mTOR pathway. An elevation ROS accompanied marker cytochrome C expression well an elevated NADH/NAD + ratio within kidneys. activity both MMP/TIMP system fibrinolytic was abnormally enhanced under conditions. Finally, we find supplementation could significantly ameliorate relevant pathological deficiency. collectively point causes damage ultimately resulting via accumulation induces

Язык: Английский

---

Radial Egg White Hydrogel Releasing Extracellular Vesicles for Cell Fate Guidance and Accelerated Diabetic Skin Regeneration

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 17, 2024

Abstract Topology and bioactive molecules are crucial for stimulating cellular tissue functions. To regulate the chronic wound microenvironment, mono‐assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue‐extracellular vesicles (radial EWH@L‐EVs). The architecture not only significantly modified gene expression of functional cells, but also achieved directional controlled release kinetics L‐EVs. Through synergy topographical inherent cues, EWH@L‐EVs effectively reduced intracellular oxidative stress promoted polarization macrophages toward an anti‐inflammatory phenotype during inflammatory phase. Afterward, facilitated centripetal migration proliferation fibroblasts endothelial cells as transitioned proliferative During latter remodeling phase, accelerated regeneration granulation tissue, angiogenesis, collagen deposition, thereby promoting reorganization wound. Compared gold standard scaffold, actively accommodated microenvironment via various functions throughout all stages diabetic healing. This can be attributed orientation topological structures molecules, which should considered utmost importance in engineering.

Язык: Английский

---

Fabrication of a 3D Corneal Model Using Collagen Bioink and Human Corneal Stromal Cells

Journal of Functional Biomaterials, Год журнала: 2025, Номер 16(4), С. 118 - 118

Опубликована: Март 28, 2025

Corneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative replacement involves fabricating artificial cornea from patient's own cells. Our study aimed to leverage bioprinting develop model using human stromal cells embedded in collagen-based bioink. We generated both cellular acellular collagen I (COL I) constructs. Cellular constructs were cultured up 4 weeks, gene expression analysis was performed assess extracellular matrix (ECM) remodeling fibrotic markers. results demonstrated significant decrease the of COL I, III III), vimentin (VIM), vinculin (VCL), indicating dynamic process towards more physiologically relevant ECM. Overall, our provides foundational framework developing customizable, replacements technology. Further research is necessary optimize bioink composition evaluate functional biomechanical properties these bioengineered corneas.

Язык: Английский

---

Isolation and Characterization of the Adamantinomatous Craniopharyngioma Primary Cells with Cancer-Associated Fibroblast Features

Biomedicines, Год журнала: 2025, Номер 13(4), С. 912 - 912

Опубликована: Апрель 9, 2025

Backgrounds: Adamantinomatous craniopharyngiomas (ACPs) are benign intracranial tumors that behave aggressively due to their location, infiltration of the surrounding nervous tissue and high capacity for recurrence. In this study, we aimed construct ACP primary cell models further investigation tumorigenic recurrent mechanisms. Methods: Primary cells were isolated from (one case) ACP. Short tandem repeat (STR) analysis was used clarify identity isolated. Whole exome sequencing (WES), immunofluorescence (IF) immunohistochemistry (IHC) performed on corresponding tissues, determine mutational profile origin phenotypic cells. Transcriptome RNA-seq obtain gene expression characteristics Subsequently, a heterotopic xenograft mouse model established confirm tumorigenesis Results: successfully cultured. The genetic variants similar original tumor tissue, they owned cancer-associated fibroblast (CAF) markers (FSP1/S100A4, Vimentin) nuclear translocation β-catenin. Meanwhile, had an level extracellular matrix components (Fibronectin). formation ability verified. transcriptional signatures also explored. Conclusions: We characterized acquired multiple CAF features demonstrated stable propagation through dozens passages. These PDC laid foundation research

Язык: Английский

---

Structure and function of vimentin in the generation and secretion of extracellular vimentin in response to inflammation

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 18, 2025

The canonical functions of vimentin in cell mechanics and migration have been recently expanded by the discovery new roles for extracellular (ECV) immune responses to infection, injury cancer. In contrast with predominantly filamentous form intracellular vimentin, ECV exists largely as soluble oligomers. release from intact cells is dependent on mechanisms that regulate assembly disassembly which are influenced discrete post-translational modifications. this review we highlight processes promote conversion insoluble filaments secretion mechanisms. Insights into regulation stromal could provide diagnostic therapeutic approaches assessing controlling inflammatory diseases.

Язык: Английский

---

EGR1‐Driven Re‐Epithelialization Enabled by Rutin‐Based Self‐Assembled Hydrogel Platform for Oral Ulcer Therapy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 28, 2025

Abstract Oral ulcer (OU) is a highly prevalent mucosal disease characterized by persistent epithelial disruption. The primary challenge in its prolonged healing process the disorder of re‐epithelialization. This study develops self‐assembled hydrogel platform based on natural small molecule rutin, which overcomes re‐epithelialization barrier through synergistic effects early growth response factor 1 (EGR1) gene programming and microenvironment remodeling. In this hydrogel, rutin formed supramolecular structures via hydrogen bonds π–π interactions without structural modification. vitro experiments confirm that rutin‐based (RUTG) possesses excellent sustained‐release properties biocompatibility. Moreover, RUTG specifically regulates transcriptional activation translation EGR1, thereby mediating expression re‐epithelialization‐related protein SOX9, ultimately accelerating cell proliferation migration as well promoting Additionally, demonstrates beneficial anti‐inflammatory antioxidant properties, effectively remodeling local microenvironment. vivo studies using an oral model further could significantly accelerate process, shorten cycle, achieve functional tissue reconstruction. Collectively, carrier‐free system, integrates with modulation to efficient re‐epithelialization, holds promise for introducing novel approaches treatment ulcers.

Язык: Английский

---