Interaction of matrix components and cells regulating cellular and molecular processes of glioma cells.

PAK6 drives tumor microenvironment remodeling in nasopharyngeal carcinoma with lymph node necrosis: implications for distant metastasis and survival.

Immune landscape and molecular regulators in renal interstitial fibrosis.

Quercetin alleviates intervertebral disc degeneration by disrupting CEBPB-HMGA1 interaction to suppress TNFA production and reduce ECM degradation.

Background The choice of an appropriate cannulation technique should be important to increase the possibility of better outcomes in terms of arteriovenous fistulas (AVF) survival and comfort of the patient undergoing hemodialysis. Methods It is a retrospective study and microarray analysis was conducted to identify differentially expressed genes (DEGs) between failing and control access samples. Sixty-four patients who underwent early cannulation (3–4 weeks after AVF creation) were enrolled and divided into two groups: a plastic cannula group (n = 33) and a metal needle group (n = 31). Comparisons were made between the groups regarding complement components, blood flow, access intimal hyperplasia, and inflammatory cell infiltration. Results (1) AVF failure occurred in 13 patients (20.3%) over a mean follow-up of 241 ± 105 days. (2) Complement B factor (CFB) levels showed significant changes within the first two weeks post-cannulation. (3) Fluctuations in CFB strongly correlated with changes in AVF blood flow during follow-up. (4) CFB variation independently predicted AVF failure, with a hazard ratio of 4.54 (95% CI, 1.21–16.99). (5) The plastic cannula group exhibited significantly lower CFB expression in both blood and outflow access, along with marked improvements in intimal hyperplasia and inflammatory cell infiltration. (6) Compared with the metal needle group, serum from the plastic cannula more significantly induced endothelial cell proliferation and nitric oxide production, with CFB playing a critical role. Conclusions The alternative complement pathway is significantly activated during initial AVF cannulation, with excessive CFB production contributing substantially to AVF failure. The use of plastic cannulas may improve long-term AVF patency by mitigating endothelial dysfunction and inhibiting inflammatory cell infiltration through suppression of CFB generation.

ANKRD46 as a shared diagnostic and therapeutic marker in keloid and type 2 diabetes mellitus identified via multi omics and experimental validation.

Nocardia seriolae infection poses a serious threat to largemouth bass (Micropterus salmoides) aquaculture, owing to the lack of effective control strategies. This study investigated the antibacterial effects and underlying mechanisms of Macleaya cordata alkaloids—sanguinarine (SE) and chelerythrine (CHE)—against N. seriolae through integrated physiological and transcriptomic approaches. Results showed SE and CHE exhibited strong in vitro antibacterial activity, with minimum inhibitory concentrations (MICs) of 62.5 and 7.8 μg/mL, respectively. In vivo trials revealed that dietary supplementation with either alkaloid significantly enhanced the survival of infected fish, yielding relative percent survival (RPS) values of 34.5% for SE and 40.0% for CHE. Concurrently, both treatments reduced bacterial load and alleviated granulomatous pathology in multiple organs, including the liver, spleen, and kidney. Physiological analyses revealed severe damage to the cell envelope, as evidenced by increased membrane permeability and structural disintegration observed under transmission electron microscopy (TEM). Transcriptomic profiling identified 3708 and 5095 differentially expressed genes (DEGs) in the SE- and CHE-treated groups, respectively, with notable downregulation of key genes involved in peptidoglycan biosynthesis, the citrate cycle, oxidative phosphorylation, and the pentose phosphate pathways. These findings demonstrate that SE and CHE inhibit N. seriolae through a multi-target mechanism simultaneously disrupting cell envelope integrity and energy production, laying the groundwork for their development as eco-friendly aquaculture therapeutics.

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder in aged people with multifaceted molecular underpinnings. It poses a severe threat to millions of older adults worldwide. The understanding of the molecular mechanisms of PD development and the performance of its therapeutic strategies has not yet reached a satisfactory level. Methods: This study integrated six transcriptomic datasets to uncover key genes (KGs) and their underlying pathogenic mechanisms, providing insights into potential therapeutic strategies for PD. We designed a comprehensive computational pipeline using various bioinformatics tools and databases to investigate PD-causing KGs, focusing on their functions, pathways, regulatory mechanisms, and potential therapeutic drug molecules. Results: In order to explore PD-causing KGs, we initially identified 303 differentially expressed genes (DEGs) between PD and control samples with 204 upregulated and 99 downregulated DEGs using the LIMMA approach with threshold values at Adj. p-value < 0.05 and abs (log2FC) ≥ 1.0. Then, protein–protein interaction (PPI) network analysis pinpointed seven top-ranked DEGs (GAPDH, PTEN, CCND1, APOE, ESR1, MAPK3/ERK1, and SNCA) as KGs or central modulators of PD pathogenesis. Regulatory network analysis of KGs identified 3 top-ranked transcription factors (FOXC1, NFKB1, and TFAP2A) and 6 microRNAs (hsa-let-7b-5p, hsa-mir-16-5p, and others) as the pivotal regulators of KGs. Gene Ontology (GO) terms and KEGG pathway enrichment analyses with KGs revealed several crucial biological processes, molecular functions, cellular components, and neurodegenerative pathways associated with the development of PD. Finally, the top five molecules guided by KGs (Nilotinib, Bromocriptine, Withaferin-A, Celastrol, and Donepezil) were identified as promising drug candidates against PD and validated computationally through ADME/T analysis and molecular dynamics simulation studies. Conclusions: The findings of this study may serve as valuable resources for developing effective treatment strategies for PD patients.

Lactylation, a recently discovered post-translational modification, has emerged as a critical regulator in cancer biology. Although chemotherapy remains the first-line treatment for metastatic colorectal cancer (CRC), only a subset of patients responds to it. This study aimed to identify key lactylation-related genes in CRC and evaluate their potential as predictive biomarkers for chemotherapy response. Gene expression profiles and corresponding clinical data from CRC patients were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were identified using the limma R package, and key modules were selected through weighted gene co-expression network analysis (WGCNA). Intersecting genes were determined by aligning DEGs with WGCNA module genes. A predictive model was developed utilizing 11 machine learning algorithms and 92 algorithm combinations. Furthermore, the correlation between lactylation-related gene score and immune infiltration as well as drug sensitivity in CRC were also investigated with "CIBERSORT" and "oncoPredict" package. Eight lactylation-related genes in CRC were identified and used to construct a predictive model employing Random Forest (RF) and Gradient Boosting Machine (GBM) algorithms. The model demonstrated strong predictive efficacy for chemotherapy response in CRC patients. Using lactylation gene scores, we effectively stratified patients into high- and low-score groups, which showed distinct patterns in immune cell infiltration, tumor mutational profile, and response to conventional antitumor drugs. Notably, the high-lactylation score group exhibited reduced Treg immune characteristics and increased sensitivity to 5-Fluorouracil. In summary, our findings demonstrate that machine learning-driven analysis of lactylation biomarkers represents a promising approach for advancing personalized therapy and optimizing clinical management in CRC.

This study aimed to elucidate the molecular mechanisms underlying cisplatin resistance in oral squamous cell carcinoma (OSCC) and to identify prognostic biomarkers that can guide personalized treatment strategies. Differentially expressed genes (DEGs) between cisplatin-sensitive and resistant OSCC cells were identified using transcriptomic data from the GSE197561 dataset. Functional enrichment analyses were conducted to explore involved pathways. Weighted Gene Co-expression Network Analysis (WGCNA) and random survival forest algorithms were employed to identify key resistance-related gene modules and hub genes. Clinical relevance was validated using The Cancer Genome Atlas (TCGA) dataset, while immune cell profiling and functional validation in SCC9/CAL27 cisplatin-resistant models were conducted to elucidate biological significance. DEGs were significantly enriched in processes such as oxidative stress response, cell cycle regulation, and immune-inflammatory pathways. WGCNA and survival analysis identified a chemotherapy resistance-associated gene module and 10 core genes, including DUSP3 and SACM1L, whose high expression was correlated with poorer overall survival. A nomogram integrating TNM stage, age, and DUSP3 expression demonstrated superior predictive performance for patient prognosis. In analyses stratified by chemotherapy resistance, upregulated DUSP3 expression appeared to synergistically cooperate with malignant tumor progression. Immune profiling revealed reduced NK cell activity and decreased populations of resting CD4⁺ memory T cells in the resistant phenotype. Functional assays confirmed that cisplatin-resistant SCC9 and CAL27 cells exhibited accelerated proliferation and epithelial-mesenchymal transition (EMT), characterized by downregulated E-cadherin and upregulated N-cadherin and Vimentin. Notably, knockdown of DUSP3 significantly reversed these resistant phenotypes. This study provides a comprehensive multi-omics-based framework for understanding cisplatin resistance in OSCC. DUSP3 was identified as a key prognostic indicator, and the proposed nomogram may enhance precision oncology efforts for cisplatin-resistant OSCC patients.

Phenotypic plasticity is a specific area of interest that refers to the ability of an organism to alter its phenotype in response to environmental changes. Adaptive visual plasticity is a fascinating phenomenon observed in various animal species. Cave-dwelling organisms often exhibit visual degeneration, but non-obligate species like Oreolalax rhodostigmatus may retain adaptive plasticity. Currently, no laboratory simulations of light-induced conditions have been reported. This study investigated the morphological, histological, and molecular responses of O. rhodostigmatus tadpoles to prolonged light exposure, hypothesizing structural retinal remodeling and upregulation of phototransduction genes reflecting reversible plasticity. Histological analysis revealed significant thickening of retinal layers (particularly inner retinal and ganglion cell layers) and structural refinement of photoreceptor outer segments in light-exposed (3- and 10-week) groups compared to dark-adapted controls (0-week). Immunohistochemistry showed restoration of organized rod and cone morphology after light exposure. Transcriptomic profiling identified 2,937-4,847 differentially expressed genes (DEGs) between groups. Key phototransduction genes (GNAT1, GRK7, CRYBA2, BEST2, MYO3B) were significantly upregulated in light-exposed tadpoles, while the cave-adaptation associated photoreceptor gene s26 was downregulated. Ultrastructural analysis indicated increased mitochondrial density and improved photoreceptor structure following light treatment. Prolonged light exposure induces significant structural, ultrastructural, and molecular adaptations in the visual organs of O. rhodostigmatus tadpoles, including retinal layer thickening, photoreceptor regeneration, and upregulation of phototransduction pathways. The downregulation of s26 and absence of mutations common in obligate cavefish suggest retained latent pathways enabling reversible plasticity, rather than irreversible degeneration. This adaptive plasticity allows non-obligate cave dwellers to balance energy conservation in darkness with functional vision restoration upon light exposure, representing a distinct evolutionary strategy compared to obligate cave species.

Genetic transmission has minimal impact on autoimmune diseases compared to environmental factors. In conclusion, studies now focus on gene expression changes for diagnosis and treatment. This study used stringent cut-off values ​​(p < 0.05, Log2(FoldChange) > 5) to monitor gene expression changes. Gene Ontology and Reactome Pathways enrichment analyses were performed, and interactions between differentially expressed genes (DEGs) were analyzed using the STRING database. Biomarker candidate genes were investigated across ten autoimmune diseases. Non-coding genes, particularly LINC01833 (upregulated in four diseases) and CD177 (upregulated in three diseases), were significant. The VCX, SLC, and KLK families were notably upregulated. Non-coding RNAs RNU5D-1 and MIR3648-1 were shared in two disease groups. Among shared genes between multiple sclerosis (MS) and ankylosing spondylitis (AS), ALPL, CHI3L1, HBM, MYL4, and PI3 were prominently downregulated. This study highlights the identification of differentially expressed signature genes across ten autoimmune diseases with high significance cut-offs (p < 0.05, Log2(FoldChange) > 5), suggesting their potential as significant targets for diagnosis and treatment.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and is characterized by high recurrence and metastasis rates. A key feature of ccRCC is its rich vascular network, which supports tumor growth and metastasis through angiogenesis, the process of forming new blood vessels. Anti-angiogenic therapy targeting the vascular endothelial growth factor (VEGF) pathway has shown efficacy in treating advanced ccRCC, but resistance often develops, highlighting the need for new therapeutic targets. We systematically screened differentially expressed genes (DEGs) between ccRCC and normal tissues using TCGA-KIRC data, and intersected them with angiogenesis-related genes from GeneCards and MSigDB. Survival analysis identified prognostic genes, and a multigene risk signature was established and validated using an independent GEO cohort (GSE29609). Functional analyses and immunohistochemistry were performed to explore the biological roles of the key gene RUNX1. A total of 27 ccRCC-related angiogenesis genes were identified, of which four formed a prognostic signature with strong predictive value. Among them, RUNX1 carried the greatest prognostic weight. Functional validation revealed that RUNX1 promotes ccRCC progression by regulating immune infiltration and lipid metabolism. In particular, RUNX1 expression was associated with enhanced CD8⁺ T-cell infiltration and upregulation of lipid metabolism genes such as FASN and SCD1. Our study identifies a novel angiogenesis-related prognostic signature for ccRCC and highlights RUNX1 as a key regulator linking tumor angiogenesis, immune infiltration, and lipid metabolism. Compared with conventional anti-VEGF therapies, targeting RUNX1 may provide broader therapeutic benefits and represents a promising translational strategy for improving ccRCC management.

BackgroundTwig blight (TB), caused by Pestalotiopsis-like species, induces twig dieback in Myrica rubra, leading to substantial economic losses in its production across China and posing a significant threat to M. rubra cultivation. To date, the immune response of M. rubra to Pestalotiopsis-like infections remains poorly understood.ResultsIn this study, full-length transcriptomics and untargeted metabolomics were employed to investigate the immune responses of resistant “Dingao” (DA) and susceptible “Dongkui” (DK) M. rubra cultivars to Pestalotiopsis pathogen infection at early (1DPI) and later (5DPI) stage. The main findings revealed that the resistant DA triggered a rapid and robust immune response at 1DPI, with 1,111 differentially expressed genes (DEGs), including 583 upregulated and 528 downregulated. As the immune response progressed to 5DPI, the number of DEGs in Dingao was reduced to 324 DEGs (114 upregulated and 210 downregulated). In contrast, the susceptible Dongkui cultivar exhibited a weak and delayed defense response. At 1DPI only 99 DEGs (26 upregulated and 73 downregulated) were identified in DK leaves; by 5DPI, a substantial shift occurred in Dongkui samples, with 3,414 DEGs (2,141 upregulated and 1,273 downregulated), showing a late but massive defense response. In Dingao samples, WRKY, AP2/ERF transcription factors (TFs) were the most upregulated TFs at the early immune response stage; by 5DPI, NAC and WRKY families became the most prominently expressed TFs. In Dongkui, notable TF upregulation (including WRKY, MYB and AP2/ERF) was only observed at 5DPI and there were not significantly expression changes at the early immune response stage. Further analysis using untargeted metabolomics revealed that Dongkui exhibited 280 upregulated and 12 downregulated differentially accumulated metabolites (DMs) at 1DPI; 503 and 166 DMs were found to be upregulated and regulated at 5DPI. In Dingao plants, 472 DMs were upregulated and 110 downregulated at 1DPI, whereas at 5DPI, 387 DMs were upregulated and 219 downregulated.ConclusionsThrough a combined analysis of full-length transcriptomics and untargeted metabolomics, we revealed distinct molecular and metabolic responses between resistant “Dingao” (DA) and susceptible “Dongkui” (DK) M. rubra cultivars under twig blight stress.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12870-025-07543-1.

Myocardial ischemia-reperfusion injury (MIRI) is a complex process leading to substantial myocardial damage. Macrophages play a pivotal role in tissue development and homeostasis. This study aimed to identify macrophage-associated biomarkers in MIRI and explore the molecular mechanisms underlying their involvement. Macrophage-related genes (MRGs) were retrieved from public databases, and differentially expressed genes (DEGs) were identified using transcriptomic data. MRGs and DEGs were integrated to identify candidate genes. Biomarkers were identified through protein-protein interaction (PPI) analysis and gene expression validation. Enrichment analysis, immune infiltration analysis, construction of molecular regulatory networks, drug prediction, and molecular docking were conducted to investigate the functional mechanisms of the identified biomarkers. Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed. Finally, single-cell data were analyzed to assess the distribution of biomarkers across annotated cell types. Tlr7, Tlr1, Tlr6, and Il33 were identified as key biomarkers. Enrichment analysis revealed that the “Ribosome,” “Oxidative phosphorylation,” and “Spliceosome” pathways were significantly enriched in these biomarkers. Immune infiltration analysis demonstrated distinct differences in the presence of macrophages, M1 macrophages, and M2 macrophages between MIRI and control groups. Notably, Tlr7, Tlr1, and Tlr6 exhibited strong positive correlations with macrophages, M1, and M2 macrophages. Biomarkers were regulated by several transcription factors (TFs) (e.g., MYC, TBP) and microRNAs (miRNAs) (e.g., -mmu-miR-15a-5p). Drug prediction and molecular docking analyses indicated that IMIQUIMOD and Acetaminophen might serve as potential therapeutic targets for MIRI. RT-qPCR confirmed significant upregulation of Tlr7, Tlr1, and Tlr6 in the MIRI group, consistent with bioinformatics findings, whereas Il33 showed no significant difference between the two groups. Five major cell types were identified, including pericytes, M2 macrophages, and M1 macrophages. Notably, Tlr7 and Tlr1 were predominantly expressed in M2 macrophages. Tlr7, Tlr1, Tlr6, and Il33 were identified as macrophage-associated biomarkers in MIRI, providing valuable insights for MIRI diagnosis and potential therapeutic interventions.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-27301-5.

Potato (Solanum tuberosum) is one of the most important global food crops. However, potato bacterial wilt, a destructive soil-borne disease caused by Ralstonia solanacearum, poses a huge threat to global potato production and quality, leading to serious economic losses worldwide. The wild potato species Solanum commersonii exhibits resistance to bacterial wilt, but the underlying molecular mechanisms remain largely obscure. In this study, we identified differentially expressed miRNAs (microRNAs), phased secondary short-interfering RNAs (phasiRNAs), along with their target transcripts, and elucidated the potential pathways involved in bacterial wilt resistance through high-throughput sequencing analyses of transcriptome, sRNAome, and degradome on normal and R. solanacearum-infected potato roots, which were collected from the susceptible diploid potato clone S. tuberosum group Phureja SP15-65 and the resistant diploid S. commersonii germplasm CM804. The results revealed that 3,434 and 1,045 differentially expressed genes (DEGs) were identified in susceptible SP15-65 and resistant CM804, respectively, with 7,652 DEGs identified between SP15-65 and CM804 upon pathogen inoculation. 23 transcripts specifically expressed in CM804 were identified to be responsive to R. solanacearum infection. Functional enrichment analysis of DEGs revealed that mitogen-activated protein kinase (MAPK) activation, reactive oxygen species (ROS) generation, calcium signaling, hormone signaling, secondary metabolism, and transcriptional reprogramming for defense were potential pathways in potato root response to R. solanacearum infection. Furthermore, 115 unique known and 147 putative novel miRNAs showed differential expression in SP15-65 or CM804 after pathogen infection. Among these differentially expressed miRNAs, some miR482, miR6024, and miR390 family members triggered the biosynthesis of phasiRNAs through the cleavage of phasiRNA-generating (PHAS) precursor transcripts, as validated by degradome-seq.The resulting phasiRNAs directed the cleavage of their downstream target mRNAs. Six miRNA-mRNA pairs and four pairs of phasiRNA-mRNA displayed negatively correlated expression changes, which may be related to bacterial wilt resistance in potato. This study sheds lights on the regulatory roles of small RNAs in potato resistance against bacterial wilt, and will provide a theoretical foundation for the cultivation of disease-resistant potato varieties.

Abies beshanzuensis is a critically endangered conifer species in the Pinaceae family, with only three wild adult trees (progenitor trees) remaining in its native habitat. To conserve its germplasm, A. beshanzuensis scions were grafted onto A. firma rootstocks, which significantly improved the growth and reproduction of the grafted plants. However, the effects of grafting on the growth and development of progeny of grafted A. beshanzuensis, as well as the underlying mechanisms, remain unclear. In this study, we compared seedling-stage growth differences between progeny of progenitor trees (PP) and grafted trees (GP), revealing significantly greater plant height and stem diameter in GP. Physiological analysis of leaf tissues showed significantly higher auxin levels in GP, increased chlorophyll content and enhanced maximum photochemical efficiency (Fv/Fm) compared to PP. De novo transcriptome assembly using PacBio and Illumina RNA-Seq identified 2,638 differentially expressed genes (DEG) between PP and GP, with significant changes in genes involved in auxin signaling and chlorophyll biosynthesis pathways in GP. Methylation-sensitive amplified polymorphism (MSAP) analysis further revealed a lower average DNA methylation level in GP compared to PP. We propose that grafting reduces DNA methylation-mediated repression of genes involved in the auxin signaling and chlorophyll synthesis, thereby enhancing seedling vigor and photosynthetic capacity. These findings provide a theoretical foundation and novel insights for the conservation of endangered woody plants, with broader implications for biodiversity preservation in the context of global climate change.

Metagenomic Next-Generation Sequencing (mNGS) enables simultaneous sequencing of both microbial and host nucleic acids in clinical samples. However, analytical approaches for interpreting complex mNGS datasets are seldom disclosed, limiting advancements in multimodal analysis and omics-driven research models built upon mNGS results. We present 402 high-quality bronchoalveolar lavage fluid mNGS DNA and RNA sequencing datasets for developing combined microbial-host metagenomic diagnostic approaches. Only the microbial (non-host) sequence reads have been deposited. We provide comprehensive descriptions of methods, tools, and pipelines used for mining microbial features (DNA/RNA microbial composition and bacteriophage abundances) and host response features (differential expression genes, transposable elements, cell-type composition, and copy number variation). These data processing pipelines set a standard for future multimodal omics diagnostic research, promoting the adoption of standardized practices in omics-based studies that integrate clinical data.

The duck meat industry is economically vital in animal husbandry; however, the genetic mechanisms governing skeletal muscle development and muscle yield remain incompletely understood. In this study, RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) in breast muscle tissues between high and low breast muscle weight (BMW) groups of Qiangying ducks. A candidate gene, CKMT2 (mitochondrial creatine kinase 2), was subsequently validated at the cellular and individual levels. RNA-seq analysis identified 540 DEGs, including 411 upregulated and 129 downregulated genes. GO and KEGG enrichment analyses revealed enrichment in fatty acid metabolism, fibrinolysis, and PPAR signaling pathways—processes closely linked to energy homeostasis and muscle growth. Functional validation demonstrated that CKMT2 overexpression significantly promoted myoblast proliferation and myotube differentiation (p &lt; 0.05), while knockdown exerted the opposite effects. At the genetic level, the GG genotype of CKMT2 SNP (G.76,602,082 G&gt;A) was associated with significantly higher BMW compared to the GA and AA genotypes (p &lt; 0.05). These findings provide novel insights into the molecular basis of muscle weight variation in meat ducks and establish CKMT2 as a key regulator of skeletal muscle growth via modulation of myoblast proliferation and differentiation. This study contributes to the theoretical foundation for improving duck muscle yield through genetic selection.

ABSTRACTMFAP5, also known as microfibrillar‐associated glycoprotein‐2 (MAGP2), may influence parameters of skin wound healing related to scar formation. To further elucidate its role in skin wound healing, we assessed skin wound repair in Mfap5−/− mice. Loss of MFAP5 reduced external wound closure, angiogenesis, and enhanced neutrophil and macrophage wound influx. Loss of MFAP5 also reduced the deposition of total and mature collagen in uninjured normal skin (NS), but not in wounds. Furthermore, NS dermis of Mfap5−/− mice was thinner without any reduction in tensile strength. Single‐cell RNA‐sequencing of NS and wounds from Mfap5+/+ and Mfap5−/− mice revealed two fibroblast subclusters that express MFAP5 more highly than other subclusters. Enrichment analysis of the differentially expressed genes (DEGs) in these two subclusters suggests these fibroblasts engage in extracellular matrix (ECM) deposition and angiogenesis. Mfap5+/+ and Mfap5−/− fibroblasts also exhibit transcriptomic differences throughout in vivo wound healing, though as healing progressed, fewer differences were evident. To examine the direct effect of MFAP5 on fibroblasts outside of the wound space, fibroblasts were isolated from Mfap5+/+ and Mfap5−/− mice for in vitro analysis. mRNA‐sequencing of Mfap5+/+ and Mfap5−/− fibroblasts found genes involved in cellular migration and proliferation, ECM synthesis, and angiogenesis to be downregulated in Mfap5−/− fibroblasts vs. Mfap5+/+ fibroblasts. Functionally, Mfap5−/− fibroblasts exhibited reduced migration, contractility, proliferation, and ECM deposition. Our findings suggest MFAP5 is a multifunctional glycoprotein in skin wound healing, as it has a role in regulating wound closure, angiogenesis, collagen deposition, inflammatory cell influx, and fibroblast behaviors related to scar formation.