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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Quercetin, a naturally occurring flavonoid, possesses anti-inflammatory properties and has emerged as a potential modulator of tissue repair. Impaired wound healing and pathological scarring are often driven by excessive inflammation and dysregulated myofibroblast differentiation. Current therapeutic approaches, however, frequently fall short in simultaneously addressing these intertwined challenges. This study investigates whether quercetin can provide a bifunctional therapeutic advantage by promoting early wound closure through inflammation resolution and suppressing scar formation via the inhibition of myofibroblast differentiation. Methods: A murine excisional wound model was employed to evaluate quercetin\u2019s effects in vivo. Mice (C57BL\/6, n = 8\/group) received daily topical applications of 1% quercetin. Wound closure kinetics were meticulously quantified using planimetry. To assess molecular and cellular changes, protein levels (CASPASE-1, interleukin-1 beta (IL-1\u03b2), alpha-smooth muscle actin (\u03b1-SMA)) and collagen III\/I ratios were determined through multiplex qPCR, RNA sequencing, western blot analysis, and histomorphometry. For in vitro investigations, human dermal BJ fibroblasts were treated with transforming growth factor beta 1 (TGF-\u03b21) (10 ng\/mL) \u00b1 quercetin (5\u201350 \u03bcM) to assess myofibroblast differentiation markers (\u03b1-SMA, collagen I) via immunofluorescence, western blot, and qPCR. Results: Quercetin significantly accelerated wound closure in vivo. The acceleration was accompanied by a reduction in the expression of IL-1\u03b2 and CASPASE-1. RNA sequencing data revealed that quercetin\u2019s anti-inflammatory effects in early wound healing involve the modulation of inflammasome complexes, including NLRP3, as well as inflammasome-mediated signaling pathways. Furthermore, treated wounds exhibited increased collagen III\/I ratios relative to control groups (p &lt; 0.05), indicative of a more regenerative matrix remodeling process. In vitro, experiments demonstrated that quercetin suppressed TGF-\u03b21-induced myofibroblast differentiation, evidenced by decreased \u03b1-SMA expression (p &lt; 0.05) and reduced collagen I synthesis. Notably, quercetin exhibited cell type-specific effects: while suppressing BJ fibroblast migration (scratch assay), it enhanced keratinocyte proliferation. This unique duality prevents aberrant myofibroblast recruitment without compromising essential epithelial coverage\u2014a critical balance for minimizing scar formation. Conclusions: Quercetin exhibits a compelling dual therapeutic role in wound healing: resolving inflammation to expedite early wound healing and inhibiting TGF-\u03b2-driven myofibroblast differentiation to attenuate scarring. By harmonizing these actions, quercetin addresses both phases of repair, positioning it as a promising candidate for scar-free wound therapy. Further efforts should focus on optimizing its bioavailability to enhance clinical translation.<\/jats:p>","DOI":"10.31083\/fbl40077","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T06:16:39Z","timestamp":1754460999000},"source":"Crossref","is-referenced-by-count":10,"title":["Dual Role of Quercetin in Promoting Early Wound Healing via Inhibiting Inflammatory Factors and Attenuating Scar Formation by Suppressing Myofibroblast Differentiation"],"prefix":"10.31083","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-5466","authenticated-orcid":true,"given":"Dan","family":"Wu","sequence":"first","affiliation":[{"name":"Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University, 200031 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5741-2344","authenticated-orcid":true,"given":"Mengyuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Plastic & Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, 200011 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5346-7566","authenticated-orcid":true,"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 200031 Shanghai, China"},{"name":"NHC Key laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, 200031 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Guo S, Dipietro LA. 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