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RNA-seq Reveals Paxillin as a Key Facilitator of Endothelial Cell Migration and Angiogenesis after Spinal Cord Injury

ABSTRACT: RNA-seq Reveals Paxillin as a Key Facilitator of Endothelial Cell Migration and Angiogenesis after Spinal Cord Injury

PROVIDER: PRJNA1161678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30677135_1.fastq.gz	Fastqsanger.gz
	SRR30677135_2.fastq.gz	Fastqsanger.gz
	SRR30677136_1.fastq.gz	Fastqsanger.gz
	SRR30677136_2.fastq.gz	Fastqsanger.gz
	SRR30677137_1.fastq.gz	Fastqsanger.gz

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RNA-seq Reveals Paxillin as a Key Facilitator of Endothelial Cell Migration and Angiogenesis after Spinal Cord Injury

Project description:Spinal cord injury (SCI) is a catastrophic condition resulting in significant neurological deficits. To map the altered pathways within the lesion epicenter and the surrounding rostro-caudal segments, we employed RNA-seq on injured spinal cord tissue. We sequenced samples from three level (rostral, epicenter, and caudal) at days 1, 14, and 28 post-injury to systematically define the transcriptomics profile, aiming to identify pathways related to angiogenesis after SCI. Gene set enrichment analysis (GSEA) revealed enriched pathways, including hepatocyte growth factor (HGF) receptor signalling and alpha-6 beta-4 signaling pathway, suggesting an active angiogenic signature. Furthermore, the participating genes in HGF receptor signaling were validated by qPCR analysis, demonstrating that HGF receptor signaling is involved in the pathological remodeling following SCI. Subsequently, we investigated paxillin as a candidate gene promoting endothelial cell migration through HGF receptor signaling. Immunohistochemistry data suggest paxillin’s role in mediating the endothelial cell migration and proliferation post-SCI. In summary, our findings indicate that paxillin is a key mediator of endothelial cell proliferation and migration in response to angiogenic factors like HGF following SCI. However, extensive mechanistic studies are required to fully establish paxillin’s role in endothelial cell migration and proliferation after SCI.

2025-05-20 | GSE277295 | GEO

Identification of circular RNAs related to vascular endothelial proliferation, migration and angiogenesis after spinal cord injury using microarray analysis

Project description:To further evaluate the role of circRNAs in SCI, we elucidated circRNA expression profiles related to vascular endothelial proliferation, migration and angiogenesis during the early stages of secondary injury in a mouse model of SCI.

2021-08-30 | GSE166967 | GEO

Phenotype screens of murine pancreatic cancer identify a Tgfa-Ccl2-paxillin axis driving human-like neural invasion

Project description:Solid cancers like pancreatic cancer (PDAC) frequently exploit nerves for rapid dissemination. This neural invasion (NI) is an independent prognostic factor in PDAC, but insufficiently modelled in genetically-engineered mouse models (GEMM) of PDAC.Here, we systematically screened for human-like NI in Europe’s largest repository of GEMM of PDAC comprising 295 different genotypes. This phenotype screen uncovered two GEMM of PDAC with human-like NI, which are both characterized by pancreas-specific overexpression of transforming-growth-factor-alpha (TGFa) and conditional depletion of p53. Mechanistically, cancer-cell-derived TGFa upregulated CCL2 secretion from sensory neurons, which induced hyperphosphorylation of the cytoskeletal protein paxillin via CCR4 on cancer cells. This activated the cancer migration machinery and filopodia formation toward neurons. Disrupting CCR4 or paxillin activity limited NI, and dampened tumor size and tumor innervation. In human PDAC, phospho-paxillin and TGFa-expression constituted strong prognostic factors. Therefore, TGFa-CCL2-CCR4-p-paxillin axis is a clinically actionable target for constraining NI and tumor progression in PDAC.

2023-10-11 | GSE245126 | GEO

Identification of circular RNAs related to vascular endothelial proliferation, migration and angiogenesis after spinal cord injury using microarray analysis

Project description:Identification of circular RNAs related to vascular endothelial proliferation, migration and angiogenesis after spinal cord injury using microarray analysis

| PRJNA702490 | ENA

Nuclear Paxillin Modulates Alternative Splicing Programs in Neurons during Sensitive Periods of Brain Development

Project description:During sensitive postnatal periods, brain neural circuits undergo significant refinement coincident with widespread neuronal alternative splicing events in which hundreds of genes alter their splice site selection to generate isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent serine119 phosphorylation of paxillin (p-paxillin S119) acts as a molecular switch in the nucleus to modulate alternative splicing during this period. We report that following NMDA receptor activation, nuclear p-paxillin S119 is recruited to nuclear speckles, where it interacts with U2AFs and splicing factors. Neuronal paxillin expression is required for timely alternative splicing of synaptic factors, including Snap25. Consequently, young mice lacking paxillin S119 phosphorylation exhibit significantly reduced levels of Snap25-5b isoforms, impaired presynaptic function at hippocampal Schaffer collateral-CA1 synapses, and deficits in short-term learning and memory. These findings support the idea that nuclear p-paxillin S119 is a critical mediator of alternative splicing programs in postnatal neurons during a sensitive period essential for neural plasticity.

2025-08-07 | GSE288599 | GEO

Paxillin regulates genomic networks in prostate cancer [LNCaP]

Project description:We report that the adaptor protein, paxillin, regulates some androgen responsive genes in the castration sensitive prostate cancer cell line, LNCaP.

2019-08-01 | GSE131726 | GEO

Paxillin regulates genomic networks in prostate cancer [PC3]

Project description:We report that the adaptor protein, paxillin, regulates some proliferative and apoptotic genes in the castration resistant prostate cancer cell line, PC3.

2019-08-01 | GSE131730 | GEO

Paxillin regulates genomic networks in prostate cancer [C4-2]

Project description:We report that the adaptor protein, paxillin, regulates some androgen responsive genes in the castration resistant prostate cancer cell line,C4-2.

2019-08-01 | GSE131728 | GEO

Nuclear Paxillin Modulates Alternative Splicing Programs in Neurons during Sensitive Periods of Brain Development

2025-08-08 | PXD060131 | Pride

Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression.

Project description:Although a number of growth factors and receptors are known to control tumor angiogenesis, relatively little is known about the mechanism by which these factors influence the directional endothelial cell migration required for cancer microvessel formation. Recently, it has been shown that the focal adhesion protein paxillin is required for directional migration of fibroblasts in vitro. Here, we show that paxillin knockdown enhances endothelial cell migration in vitro and stimulates angiogenesis during normal development and in response to tumor angiogenic factors in vivo. Paxillin produces these effects by decreasing expression of neuropilin 2 (NRP2). Moreover, soluble factors secreted by tumors that stimulate vascular ingrowth, including vascular endothelial growth factor (VEGF), also decrease endothelial cell expression of paxillin and NRP2, and overexpression of NRP2 reverses these effects. These results suggest that the VEGF-paxillin-NRP2 pathway could represent a new therapeutic target for cancer and other angiogenesis-related diseases.

| S-EPMC3986673 | biostudies-literature

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