Fibroblast Migration Research Articles (Page 1)

USP7 inhibition promotes wound healing by suppressing M1 macrophage polarization via NF-κB/MAPK signaling pathway.

Oral submucous fibrosis (OSF) is a precancerous condition primarily caused by arecoline in betel nuts. The transforming growth factor (TGF)-β/mothers against decapentaplegic homolog 3 (Smad3) signaling pathway plays a pivotal role in its pathogenesis. This study explores the interaction between tropomyosin-1 (TPM1) and STIP1 homology and U-Box-containing protein 1 (STUB1) in regulating this pathway and its impact on OSF progression. We found that arecoline dose and time-dependently upregulates the expression of TPM1 mRNA and protein in human oral fibroblasts (HOrF). Treating HOrF with 20μg/mL arecoline for 48h could effectively drive fibroblast proliferation, fibrosis, migration and invasion. TPM1 knockdown reversed these effects. Mechanistically, arecoline upregulates TPM1 by activating the TGF-β/Smad3 signaling pathway. Notably, TPM1 overexpression rescued TGF-β/Smad3 activity even in the presence of the TGF-β inhibitor SB431542, revealing a positive feedback loop. Additionally, Western blotting and co-immunoprecipitation (Co-IP) analyses showed that arecoline downregulates STUB1, thereby inhibiting the ubiquitination of TGF-β/Smad3 in HOrF. Meanwhile, TPM1 competitively binds to STUB1, blocking its interaction with TGF-β/Smad3 and thereby stabilizing the pathway, which exacerbates fibrosis. Statistical analysis (one-way ANOVA with Tukey's HSD post-hoc test or independent-samples t-test) confirmed the significance of all major findings (p < 0.05). In conclusion, activation of the TGF-β/Smad3 pathway upregulates TPM1, which in turn blocks STUB1-mediated ubiquitination of the same cascade, establishing a positive-feedback loop that exacerbates arecoline-induced OSF. These findings improve our understanding of OSF's molecular pathogenesis and offer a potential target for its prevention and treatment.

Rehmannin attenuates bleomycin-induced pulmonary fibrosis via THBS4-dependent modulation of fibroblast-dendritic cell interplay and matrix dynamics.

Introduction Wound healing and skin regeneration have become global health challenges, causing substantial harm to the physical and mental health. Many studies have shown that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) can promote tissue repair and regeneration. However, the efficacy and underlying mechanisms of hUCMSC-Exos in treatment remain to be elucidated. Methods hUCMSC-Exos were isolated by ultracentrifugation and characterized by analyses of nanoparticle tracking analysis (NTA), western blotting (WB), and transmission electron microscopy (TEM). The efficacy of hUCMSC-Exos on the proliferation, migration, and angiogenesis potential of fibroblasts and endothelial cells were examined in vitro . The effects of the hUCMSC-Exos on wound healing were assessed by wound closure rate, histological and immunohistochemical analyses. miRNAs and their target genes that may play a role in skin repair and regeneration were identified and predicted through bioinformatics analysis. Results In vitro analysis indicated that hUCMSC-Exos are easily internalized by human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs), significantly promoting the proliferation and migration of HSFs, as well as the proliferation and tube formation of HUVECs. Analysis of skin wound models indicated that hUCMSC-Exos significantly accelerate wound healing by reducing inflammation, stimulating angiogenesis, and promoting the formation of extracellular matrix. Mechanistically, bioinformatics analysis suggests that Unc-51-like autophagy activating kinase 2 (ULK2), Collagen Type XIX Alpha 1 Chain (COL19A1), and Interleukin-6 Signal Transducer (IL6ST) are potential key molecules involved in the regulation of wound repair by hUCMSC-Exos. Discussion In summary, hUCMSC-Exos regulate the functions of HUVEC and HSFs through miRNA, significantly promoting wound healing and tissue repair, suggesting that hUCMSC Exos therapy is a promising therapeutic approach.

Bioactive peptide HX-12C enhances fibroblast function through TGF-β/Smad signaling pathway and promotes wound healing in vitro and in vivo.

Evaluation of the combined effects of photobiomodulation therapy and periodontal ligament stem cell-derived exosomes on the proliferation and migration of human gingival fibroblasts: An in vitro study.

Suppression of MERTK inhibits proliferation and migration of pterygium fibroblasts.

Controlled release of ionic carrier hydrogels for sequential immunomodulation to facilitate stage-specific treatment of infectious wound.

Targeting HMGB1 modulates cancer-associated fibroblasts and enhances radiotherapy in lung adenocarcinoma.

In situ forming silk fibroin hydrogel dressing accelerates acute wound healing via immunomodulation and extracellular matrix regeneration.

Circular RNA-based therapy provides sustained and robust expression of FGF2 to accelerate diabetic wound healing.

Asiatic acid inhibits keloid fibroblast migration and collagen deposition via suppression of STAT3 activation.

Electronic cigarette (e-cig) aerosol encounters all constituents in users' mouths, including soft and hard tissues and dental implants. Deposition of the e-cig aerosols on dental implants can lead to implant failure (peri-implantitis). This study aims to evaluate the effect of e-cig vaping on the interactions of normal and diabetic human fibroblasts with dental implant materials. Human gingival and diabetic skin fibroblasts were cultured on titanium (Ti-6Al-4V and Ti-6Al-4V-nitride) dental implant disks and exposed for 10 min, twice a day, to e-cig aerosol containing 12 mg/ml of nicotine. Twenty-four hours post-exposure, we evaluated the effects of the e-aerosol on fibroblast adhesion, growth, migration, collagen contractility, and cell apoptosis/necrosis. The e-cig aerosol significantly decreased adhesion (p < 0.01). This effect was observed in both normal gingival and diabetic skin fibroblasts. There was also a significant (p < 0.01) decrease in cell viability/proliferation of gingival and diabetic skin fibroblasts on dental implant materials following exposure to e-cig aerosol. The cell migration assay demonstrated that e-cig aerosol delayed wound healing after monolayer cell damage. Collagen contraction assay demonstrated that e-cig aerosol decreased the contractile capacity of gingival and diabetic skin fibroblasts. The adverse effect of e-cig aerosol on human fibroblasts involves the apoptotic/necrotic pathway, as the apoptotic cell rate increased from 0.75% in the control to 5.25% in gingival fibroblasts exposed to e-cig aerosol. A similar observation was made with diabetic skin fibroblasts. This study demonstrated, for the first time, possible adverse effects of e-cig aerosol on the interactions between gingival and diabetic skin fibroblasts and dental implants. This study suggests that e-cigs may pose a potential risk to oral health. Clinicians providing dental care to patients with dental implants should consider special care when patients vape. Also, e-cig users should consider an accurate mouth hygiene plan to prevent periodontal disease.

Background: Peperomia pellucida leaf extract have been claimed for antioxidant, antimicrobial, cytotoxic, and wound-healing effects. Aim: The objective of this study was to explore the phytochemical composition and assess the antioxidant, antibacterial, cytotoxic, and wound-healing properties of leaf extracts from P. pellucida, which were obtained using petroleum ether, chloroform, and methanol. Methods: Bioactive substances were identified by quantitative and qualitative phytochemical investigations. The chemical components were further analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). The DPPH radical scavenging assay was used to measure antioxidant activity. The evaluation of antibacterial activity was conducted using inhibition zone assays targeting bacterial pathogens. The MTT assay was employed to evaluate cytotoxicity in L929 fibroblast cells. The properties related to wound healing were examined through in vitro scratch assays. Results: The methanol extract demonstrated the greatest variety and abundance of bioactive compounds, encompassing alkaloids, flavonoids, tannins, phenols, and terpenoids. The results indicated notable antioxidant activity (IC50 = 75.4 μg/mL) that is comparable to that of ascorbic acid. Antibacterial assays demonstrated significant inhibition zones ranging from 15 to 17 mm. The methanol extract showed no toxicity at concentrations up to 125 μg/mL in cytotoxicity assays and facilitated fibroblast migration and proliferation in wound-healing studies. Conclusion: The results indicate that the methanolic extract of P. pellucida leaves exhibits significant pharmacological effects, especially in relation to antibacterial uses and the promotion of wound healing. The results highlight its promise as a significant natural resource for therapeutic applications. Major Findings: The methanolic extract of P. pellucida was rich in bioactive phytochemicals and exhibited strong antioxidant and antibacterial activities. It was non-toxic to fibroblast cells and promoted their migration, suggesting significant wound-healing potential.

The rising prevalence of multidrug-resistant wound infections demands innovative therapeutic strategies that simultaneously eradicate pathogens and orchestrate the complex immune healing process. This study presents an innovative green strategy for the in situ anchoring of ultrasmall (1.26 ± 0.3 nm), highly dispersed silver nanoparticles (AgNPs) on attapulgite (APT) nanorods mediated by a Paeonia lactiflora Radix extract. The resulting AgNPs/APT nanocomposite was further integrated into the physically cross-linked network of carboxymethyl chitosan (CMC) and κ-carrageenan (KCG) to fabricate a multifunctional composite cryogel (CMC/KCG/AgNPs/APT). The composite cryogel exhibited enhanced antibacterial efficacy against multidrug-resistant bacteria and biofilms and a well-balanced combination of mechanical strength, rapid fluid absorption, and biocompatibility, resulting from the dual role of APT in conferring mechanical robustness to the polymer matrix and confining the size of AgNPs to the ultrasmall regime for augmented biological functions. Moreover, this composite cryogel demonstrated unique properties of polarizing the pro-inflammatory M1 phenotype into the pro-healing M2 phenotype with CD163+ cells increasing by 2.6 times, effectively inhibiting inflammatory factors (TNF-α and iNOS) and promoting fibroblast migration. In a full-thickness skin defect model infected with A. baumannii, this multimodal synergy culminated in a significantly enhanced wound healing rate of 95.34 ± 2.9% within 14 days. This study proposes a novel strategy that synergistically integrates metal nanomaterials, natural clay, and biological polysaccharides, thereby offering a promising solution to the longstanding issues of antibacterial efficacy, biological safety, and immune regulation balance in infected wound management.

Study on the biological effects and mechanisms of demineralized dentin matrix on human gingival fibroblasts.

Abstract Inula viscosa (L.) Aiton is a traditional medicinal plant extensively utilized in Mediterranean nations for the treatment of rheumatic pain, inflammatory disorders, diabetes, anemia, and cancer. This study further explored its anti‐inflammatory mechanisms through the highest components, chlorogenic acid, rosmarinic acid, and rutin, on the expression of the ionized calcium‐binding adapter molecule 1 (Iba1) on monocyte‐derived macrophage‐like cells. Iba1 is known to contribute pathogenesis of diverse inflammatory diseases. HPLC analysis identified 13 major phenolic compounds, with rosmarinic acid, chlorogenic acid, and rutin as major components. The aqueous extract of the plant and its major components exhibited dose‐dependent antiproliferative activity on pTHP‐1, RAW264.7, and PCS‐201–012 cells. Immunofluorescence staining revealed a significant reduction in Iba1 protein expression, which is associated with inflammation, at the high dose of I. viscosa and rutin. Molecular docking studies indicated that rosmarinic acid and rutin had the strongest predicted interactions with Iba1, with docking scores of −12.403 and −12.301 kcal/mol and MM/GBSA binding energies of −64.47 and −84.20 kcal/mol, respectively. I. visoca and its major components were observed to significantly suppress iNOS activity in LPS‐stimulated cells; these findings were also supported by RT‐PCR results. Treatment with the high dose of I. viscosa resulted in 9.45% necrotic cells and caused cell cycle arrest in the S phase (59.2 ± 5.23%). This suggests that it may potentially reduce the proliferation of activated macrophages. In the fibroblast migration assays, the relative wound closure rate was found to be significant 27.06 ± 18.09% at the low dose of I. viscosa and 31.59 ± 22.42% at the high dose of I. viscosa . Although the relatively low wound closure rate limits tissue repair, it may benefit chronic wounds and fibrosis by suppressing excessive cell proliferation and inflammation. These results suggest that I. viscosa is a promising natural source of bioactive compounds with potential applications in anti‐inflammatory drug development.

Diabetic wounds exhibit excessive endoplasmic reticulum stress (ERS), which can lead to fibroblast dysfunction, abnormal natural killer (NK) cell activation, and imbalanced macrophage polarization. ERS exerts a bidirectional regulatory effect on wound fibroblasts and immune cells; simply inhibiting ERS impedes wound tissue regeneration. Existing hydrogels cannot precisely regulate ERS and synergistically repair multicell functional defects. Monocyte Chemoattractant Protein-1 (MCP-1), synthesized by fibroblasts in diabetic wounds, is a key molecular regulator of ERS and fibroblast function and a hub for fibroblast-immune cell interactions. This study constructed histidine–chitosan–fibroblast growth factor receptor (FGFR) agonist peptide 1 (FAP1)–pGPU6/GFP/Neo MCP-1–shRNA plasmid (HCFD) nanoparticles. The HCFD nanoparticles were loaded onto 3-carboxyphenylboronic acid (PBA)-modified methyl acrylate gelatin (GelMA) hydrogel (GP), forming the nanocomposite hydrogel Gel–PBA–HCFD (GPHCFD). The GPHCFD nanocomposite hydrogel utilizes FAP1 to target FGFR on wound fibroblasts. Under conditions of excessive ERS, GPHCFD nanocomposite hydrogels were triggered to break boric acid bonds and protonate histidine imidazole, thereby achieving the precise release of the plasmid, which could stably knock out the MCP-1 gene in fibroblasts. Notably, GPHCFD exhibited excellent ERS-responsive functionality, significantly reducing MCP-1 expression and alleviating excessive ERS in fibroblasts under in vitro thapsigargin (Tg)-induced high ERS conditions and high ERS environments in diabetic wounds. GPHCFD improved fibroblast proliferation, migration, and collagen secretion functions. Furthermore, GPHCFD inhibited inflammatory factors of NK cells, including TNF-α and IFN-γ, as well as the aberrant proliferation of CD45+CD3−NK1.1+ NK cells by reducing the MCP-1-mediated activation of the CCR2 receptor on NK cells and ERS. Additionally, CD45+CD3−NK1.1+CD11b− NK cells were encouraged to differentiate into mature CD45+CD3−NK1.1+CD11b+ NK cells by GPHCFD. Additionally, the GPHCFD nanocomposite hydrogel reduced the MCP-1-mediated activation of the CCR2 receptor on macrophages, thereby decreasing excessive ERS in macrophages and driving their polarization from M1-type CD68+iNOS+ cells to M2-type CD68+CD206+ cells. This GPHCFD nanocomposite hydrogel integrates ERS-responsive nanoparticle release, fibroblast gene editing, and immune reprogramming, offering a new therapeutic modality for diabetic wounds incorporating tissue regeneration–immune homeostasis synergistic regulation.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s12951-025-03732-0.

An in-depth evaluation of fucoidans from five brown seaweeds for wound healing and cytoprotection: analyses of bioactivities and cellular mechanisms.

Houttuynia cordata essential oil (HCEO) is a promising ingredient for acne-focused phytocosmetics. This in vitro study evaluated its volatile compounds, antimicrobial, antioxidant, wound-healing, anti-melanogenic, and anti-inflammatory properties, along with the stability of topical oil‑in‑water emulsions. GC-MS analysis identified n-decanoic acid (46.21%), β-myrcene (14.082%), and 2-undecanone (11.01%) as the main components. HCEO inhibited the growth of Staphylococcus aureus, Candida albicans, Staphylococcus epidermidis, and Cutibacterium acnes. It displayed antioxidant activity, with IC50 values of 13.25 ± 0.09 mg/mL (DPPH) and 17.44 ± 0.16 mg TEAC/g (FRAP). No cytotoxicity was observed in NIH/3T3 fibroblasts and RAW 264.7 macrophages (up to 500 µg/mL). HCEO enhanced fibroblast migration by 26.94% ± 1.12% at 400 µg/mL. It inhibited melanin synthesis in B16F10 and A375 cells, with IC50 values of 200.61 ± 2.19 and 152.16 ± 1.97 µg/mL, respectively, and tyrosinase activity (IC50 of 48.00 ± 0.01 µg/mL). Additionally, HCEO suppressed nitric oxide production in LPS-stimulated macrophages (IC50 of 1.176 ± 0.084 µg/mL). Oil-in-water emulsions containing HCEO maintained physical stability for eight weeks, indicating suitability for cosmetic product development. These findings suggest HCEO has potential as a natural ingredient for advanced skincare formulations targeting acne and skin inflammation, although further work is needed to optimise loading, assess skin permeation, and confirm efficacy in vivo.