ArticleCell communication and signaling : CCS2013
Inhibition of a novel specific neuroglial integrin signaling pathway increases STAT3-mediated CNTF expression.
Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF.Stem cells (Dayton, Ohio) · 2026Article
- Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury.Stem cells (Dayton, Ohio) · 2025Article
- Astrocyte focal adhesion kinase reduces passive stress coping by inhibiting ciliary neurotrophic factor only in female mice.Neurobiology of stress · 2024Article
- The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein.Science advances · 2023Article
- Axotomy results in an increase in Thy-1 protein in the 35-day-old rat supraoptic nucleus.Experimental brain research · 2023Article
- Neuroprotective astroglial response to neural damage and its relevance to affective disorders.Exploration of neuroprotective therapy · 2023Article
- Role of Vitronectin and Its Receptors in Neuronal Function and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Female-specific neuroprotection after ischemic stroke by vitronectin-focal adhesion kinase inhibition.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice.Physiological reports · 2022Article
- LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting.Frontiers in cellular neuroscience · 2022Article
- PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.Cell communication and signaling : CCS · 2021Article
- A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles.European journal of medicinal chemistry · 2021Article
- MiR-9-5p Regulates Genes Linked to Cerebral Calcification in the Osteogenic Differentiation Model and Induces Generalized Alteration in the Ion Channels.Journal of molecular neuroscience : MN · 2021Article
- FAK inhibitors as promising anticancer targets: present and future directions.Future medicinal chemistry · 2021Review
- Astrocytic role of Thy-1 induced inhibition of axonal sprouting.Neural regeneration research · 2021Article
- Inhibition of focal adhesion kinase increases adult olfactory stem cell self-renewal and neuroregeneration through ciliary neurotrophic factor.Stem cell research · 2020Article
- Article
- Protective Functions of Reactive Astrocytes Following Central Nervous System Insult.Frontiers in immunology · 2020Review
- Review
- Vitronectin from brain pericytes promotes adult forebrain neurogenesis by stimulating CNTF.Experimental neurology · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCiliary neurotrophic factor (CNTF) expression is repressed in astrocytes by neuronal contact in the CNS and is rapidly induced by injury. Here, we defined an inhibitory integrin signaling pathway.
resultsThe integrin substrates laminin, fibronectin and vitronectin, but not collagen, thrombospondin or fibrinogen, reduced CNTF expression in C6 astroglioma cells. Antibodies against αv and β5, but not α6 or β1, integrin induced CNTF. Together, the ligand and antibody specificity suggests that CNTF is repressed by αvβ5 integrin. Antibodies against Thy1, an abundant neuronal surface protein whose function is unclear, induced CNTF in neuron-astrocyte co-cultures indicating that it is a neuroglial CNTF repressor. Inhibition of the integrin signaling molecule Focal Adhesion Kinase (FAK) or the downstream c-Jun N-terminal kinase (JNK), but not extracellular regulated kinase (ERK) or p38 MAPK, greatly induced CNTF mRNA and protein expression within 4 hours. This selective inhibitory pathway phosphorylated STAT3 on its inhibitory ser-727 residue interfering with activity of the pro-transcription Tyr-705 residue. STAT3 can activate CNTF transcription because it bound to its promoter and FAK antagonist-induced CNTF was reduced by blocking STAT3. Microinjection of FAK inhibitor directly into the brain or spinal cord in adult mice rapidly induced CNTF mRNA and protein expression. Importantly, systemic treatment with FAK inhibitors over 3 days induced CNTF in the subventricular zone and increased neurogenesis.
conclusionsNeuron-astroglia contact mediated by integrins serves as a sensor to enable rapid neurotrophic responses and provides a new pharmacological avenue to exploit the neuroprotective properties of endogenous CNTF.
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