Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA136837 | ENA |
REPOSITORIES: ENA
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Project description:Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
2011-01-14 | GSE26390 | GEO
Project description:Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies. Wildtype murine tissue was harvested at either day 6 or 14 post-injury following 48 hours or 10 days of mechanical loading, respectively (n=4 mice per group per time point). Murine RNA was isolated, labeled, and hybridized to the GeneChip microarray according to the manufacturer’s protocols (Affymetrix, Santa Clara, CA, USA). Each gene in the microarray was represented by 20 oligonucleotide pairs, with each pair consisting of an oligonucleotide perfectly matched to the cDNA sequence, and a second oligonucleotide containing a single base mismatch. Raw microarray data (sample intensity files) were processed using GeneSpring GX 11.0 (Agilent Technologies Inc., Santa Clara, CA, USA).
2011-01-14 | E-GEOD-26390 | biostudies-arrayexpress
Project description:Fibrosis is a pathological process characterized by persistent fibroblast activation and excessive extracellular matrix (ECM) accumulation. Aortic carboxypeptidase-like protein (ACLP), an ECM-associated protein that binds fibrillar collagen, is upregulated in fibrotic tissues and promotes fibroblast differentiation through canonical TGFβ receptor I signaling. We hypothesized that when presented within the collagen matrix, ACLP engages mechanically driven signaling pathway that contribute to fibroblast activation. Here, we identified a previously unrecognized mechanism through which collagen-bound ACLP activates fibroblasts via β1 integrin-mediated signaling. Collagen-bound ACLP induced rapid fibroblast spreading, increased β1 integrin activation, and promoted focal adhesion maturation. These early adhesion events were followed by elevated activation of the GTPases RhoA and Rac1, with enhanced F-actin assembly and nuclear accumulation of myocardin-related transcription factor A (MRTFA), a key regulator of activated fibroblast gene expression. Transcriptomic profiling revealed enrichment of focal adhesion, ECM–receptor interaction, and actin cytoskeletal gene pathways in response to collagen-bound ACLP. These findings establish collagen-bound ACLP as an ECM-derived cue that links matrix composition to fibroblast activation pathways.
2026-03-31 | GSE312027 | GEO
Project description:Fibrosis is a pathological process characterized by persistent fibroblast activation and excessive extracellular matrix (ECM) accumulation. Aortic carboxypeptidase-like protein (ACLP), an ECM-associated protein that binds fibrillar collagen, is upregulated in fibrotic tissues and promotes fibroblast differentiation through canonical TGFβ receptor I signaling. We hypothesized that when presented within the collagen matrix, ACLP engages mechanically driven signaling pathway that contribute to fibroblast activation. Here, we identified a previously unrecognized mechanism through which collagen-bound ACLP activates primary stromal cells towards a myofibroblast phenotype via β1 integrin-mediated signaling. Collagen-bound ACLP induced rapid fibroblast spreading, increased β1 integrin activation, and promoted focal adhesion maturation. These early adhesion events were followed by elevated activation of the GTPases RhoA and Rac1, with enhanced F-actin assembly and nuclear accumulation of myocardin-related transcription factor A (MRTFA), a key regulator of activated fibroblast gene expression. Transcriptomic profiling revealed enrichment of focal adhesion, ECM–receptor interaction, and actin cytoskeletal gene pathways in response to collagen-bound ACLP. These findings establish collagen-bound ACLP as an ECM-derived cue that links matrix composition to fibroblast activation pathways.
2026-03-31 | GSE324887 | GEO
Project description:The allostatic adaption VSMCs to a mechanical perturbation relies on the interaction of the CSK contractile components to generate cellular force, as well as the engagement of the mechanosensitive signaling elements, i.e. the interplay among mechanosensitive ion channels, integrin-focal adhesion-actin axis, and calcium signal that convert the mechanical input into cellular contractile response We used miroarray to analyze the biophysical mechanisms underlying aging-associated decline in mechanosensation and VSMC functions
2023-11-01 | GSE243736 | GEO
Project description:Mechanical force has been shown to regulate periodontal ligament cells (PDLs) behaviors. However, different force types lead to distinct PDLs’ responses. Here, the differential gene expression profiling of PDLs subjected to static and intermittent compressive forces was examined using RNA sequencing technique. Results demonstrated that the static and intermittent compressive force treated PDLs exhibited the differential regulation genes. KEGG pathway enrichment analysis revealed that focal adhesion and transforming growth factor beta signaling pathway were commonly upregulated while calcium signaling pathway was downregulated in both static and intermittent compressive force-treated PDLs. Interestingly, Wnt signaling pathway was upregulated only in the PDLs that subjected to the intermittent compressive force.
2019-07-23 | GSE112122 | GEO
Project description:We performed single-cell RNA sequencing on skin, wounded tissue, or wounded tissue subjected to mechanical strain. Wounds could be treated with focal adhesion kinase inhibitor (FAKI) hydrogels or in mice with FAK knocked out in the myeloid cells.
2025-05-17 | GSE297064 | GEO
Project description:Purpose: mechanical homeostasis is a crucial process for Humen dermal fibroblast cell (HDFs) survival and functionality. Cell can sense environmental change and modify the expression of extracellular matrix, focal adhesion and cytoskeleton protein to maintain the correct mechanical homeostasis. In this study we observed change in microRNA levels linked with mechanical response. HDFs were seeded for 48 our on PDMS 3 kPa and 30 kPa substrate coating with fibronectin to simulate "soft" and "stiff" substrate, then sRNA-seq was performed.
2019-03-31 | GSE123008 | GEO