Immediate Early Gene c-fos in the Brain: Focus on Glial Cells

Cruz-Mendoza, Fernando; Jáuregui-Huerta, Fernando; Aguilar-Delgadillo, Adriana; Garcı́a-Estrada, Joaquı́n; Luquı́n, Sonia

doi:10.3390/brainsci12060687

Cited by 46 publications

(29 citation statements)

References 155 publications

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“…Therefore, we selected vertical retinal sections through the ONH to observe astrocyte activation. The c‐Fos gene, which is a rapidly activated in stimulated cells, was used as a neural activity marker (Cruz Mendoza et al, 2022). Compared with sham‐operated control retinas (Ctr), c‐Fos‐positive fluorescence signals progressively increased in GFAP‐labeled astrocytes found in COH retinas from G4d to G4w (indicated with arrow heads, Figure 4b3–f3).…”

Section: Resultsmentioning

confidence: 99%

Modulation of Rac1/PAK1/connexin43‐mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma

Zhao

Zhou

Guo

et al. 2023

Glia

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Background: Connexin43 (Cx43) is one of major gap junction proteins in glial cells. Mutation in the gap junction protein alpha 1 gene of Cx43 has been detected in human glaucomatous retinas, suggestive of involvement of Cx43 in pathogenesis of glaucoma. However, the role of Cx43 in glaucoma has not been clearly elucidated.Methods: A mouse model of chronic ocular hypertension (COH) was produced by injecting magnetic microbeads into the eye anterior chamber. To explore the role of Rac1 in regulating Cx43 function, Rac1 conditional knockout in astrocytes was generated by subretinal injection of AAV-GFAP-Cre in Rac1 flox/flox mice. The hemichannel activity was assayed by ethidium bromide uptake. The level and source of ATP were assayed by a commercial ATP assay kit, ATP sensors and removing microglia.Results: In this study, we showed that Cx43 were mainly expressed in retinal astrocytes. Intraocular pressure (IOP) elevation induced astrocyte activation, as evidenced by increased expressions of c-Fos and glial brillary acidic protein (GFAP), which results in downregulation of Cx43 and changes of Cx43 phosphorylation at Ser373 and Ser368 sites. In the optic nerve head of COH mice, Cx43 expression in Gap43 (an activity-dependent plasticity protein) positive astrocytes was reduced. In COH retinas, Rac1, a member of the Rho family, was activated, which was consistent with the decrease of Cx43 expression in a time course. Pharmacological inhibition of Rac1 inhibited the activity of its downstream molecule PAK1, and reversed the reduction of Cx43 expression and astrocyte activation induced by IOP elevation. Co-immunoprecipitation experiments further demonstrated the interactions between Cx43 and active Rac1 or p-PAK1. Inhibition of Rac1 or conditional knockout of Rac1 in macroglial cells increased the ATP release through Cx43 hemichannels in astrocytes of COH retinas. Additionally, Rac1 deletion in astrocytes upregulated the expression of adenosine A3 receptor in retinal ganglion cells (RGCs) and promoted RGC survival, at least at early stage of IOP elevation through activating adenosine receptors.Conclusions: Our results showed that Rac1 in astrocytes regulated glaucomatous RGC survival through Cx43-mediated ATP release. These ndings suggest that modulation of Rac1/PAK1/Cx43 pathway in astrocytes may be a potential strategy of neuroprotection in glaucoma.

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Section: Resultsmentioning

confidence: 99%

Modulation of Rac1/PAK1/connexin43‐mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma

Zhao

Zhou

Guo

et al. 2023

Glia

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“…However, the role of miR-150-5p in the course of EV-D68 infection remains unknown and needs to be investigated. The c-Fos proto-oncogene was initially identified as the gene responsible for Finkel-Biskis-Jinkins murine sarcoma virus-induced bone cancers ( Cruz-Mendoza et al, 2022 ). Fos, however, is a protein that can operate as either a transcription factor or a transrepressor.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA SNHG9 regulates viral replication in rhabdomyosarcoma cells infected with enterovirus D68 via miR-150-5p/c-Fos axis

et al. 2023

Front. Microbiol.

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BackgroundThe Enterovirus D68 (EV-D68) epidemic has increased knowledge of the virus as a pathogen capable of causing serious respiratory and neurological illnesses. It has been shown that long noncoding RNAs (lncRNAs) regulate viral replication and infection via multiple mechanisms or signaling pathways. However, the precise function of lncRNAs in EV-D68 infection remains unknown.MethodsThe differential expression profiles of lncRNA in EV-D68-infected and uninfected rhabdomyosarcoma (RD) cells were studied using high-throughput sequencing technology. The knockdown through small interfering RNA (siRNA) and overexpression of lncRNA SNHG9 (small ribonucleic acid host gene 9) were applied to investigate how lncRNA SNHG9 regulates EV-D68 propagation. The targeted interactions of lncRNA SNHG9 with miR-150-5p and miR-150-5p with c-Fos were validated using dual luciferase reporter system. LncRNA SNHG9 knockdown and miR-150-5p inhibitor were co-transfected with RD cells. QRT-PCR and western blot were used to detect RNA and protein levels, of c-Fos and VP1, respectively. Median tissue culture infectious dose (TCID50) was applied to detect viral titers.ResultsThe results demonstrated that a total of 375 lncRNAs were highly dysregulated in the EV-D68 infection model. In the EV-D68 infection model, lncRNA SNHG9 and c-Fos were increased in EV-D68-infected RD cells. However, the expression level of miR-150-5p was downregulated. In addition, overexpression of SNHG9 in RD cells resulted in decreased viral replication levels and viral titers following infection with EV-D68, and further experiments revealed that overexpression of SNHG9 inhibited the viral replication by targeting increased miR-150-5p binding and significantly increased c-Fos expression in RD cells.ConclusionOur findings indicate that the SNHG9/miR-150-5p/c-Fos axis influences EV-D68 replication in host cells and that SNHG9 may be a possible target for anti-EV-D68 infection therapies.

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“…As both groups of animals were similarly sensitive to responding to stimuli in the peripheral visual field (information that may be reflected in posterior SC), the current study lacks the ability to clearly interpret the reduced posterior c-Fos levels in posterior adult SC during stimulus presentation. As c-Fos expression levels may reflect local responses to growth factors or neuromodulation, or may be localized to other cell types besides neurons, 38 it will be important in future physiological studies of SC activity to compare the anterior- and posterior-most responses over development during this behavior.…”

Section: Discussionmentioning

confidence: 99%