Lipocalin-2 and Cerebral Stroke

Luo, Chao; Zhou, Shuai; Yin, Shibin; Jian, Lipeng; Luo, Pengren; Dong, Jigeng; Liu, Erheng

doi:10.3389/fnmol.2022.850849

Cited by 11 publications

(7 citation statements)

References 119 publications

(174 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipocalin-2, which among its many functions can act as a inducer of chemokine expression [ 43 – 45 ], was identified as one of the DEG most highly responsive to RD, with a 42.9-fold increase at 1 dprd in the RNA-Seq analysis. We therefore chose to validate Lcn2 mRNA results and examine LCN2 protein expression.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment

Abcouwer,

Miglioranza Scavuzzi,

Kish

et al. 2024

J Neuroinflammation

View full text Add to dashboard Cite

The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Interestingly, Lcn2, which has been implicated in induction of cytokine expression [ 43 – 45 ], was also very highly upregulated in the detached RPE. Greatly increased expression of Lcn2 mRNA in the detached RPE at 1 dprd was confirmed.…”

Section: Discussionmentioning

confidence: 99%

The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment

Abcouwer,

Miglioranza Scavuzzi,

Kish

et al. 2024

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Although this is not an MC medium condition-specific event, LCN2 expression was only induced upon IL-1β stimulation when the cells were in a spheroid state. Astrocyte-derived LCN2 is involved in chronic itch [ 37 ], cerebral stroke [ 38 , 39 ] and so on. To reveal the role of LCN2 in these diseases, IL-1β-dependent and TNF-α independent induction mechanism of the of HASTR/ci35 spheroids might be a useful tool.…”

Section: Resultsmentioning

confidence: 99%

Rapid and Stable Formation Method of Human Astrocyte Spheroid in a High Viscous Methylcellulose Medium and Its Functional Advantages

et al. 2023

View full text Add to dashboard Cite

Astrocytes, a type of glial cell in the brain, are thought to be functionally and morphologically diverse cells that regulate brain homeostasis. Cell immortalization is a promising technique for the propagation of primary human astrocytes. The immortalized cells retain their astrocytic marker mRNA expression at lower levels than the primary cells. Therefore, improvement of the differentiation status is required. The use of a 3D formation technique to mimic structural tissue is a good strategy for reflecting physiological cell–cell interactions. Previously, we developed a spheroid formation method using highly viscous methyl cellulose (MC) medium. In this study, we applied this formation method to the well-established immortalized human astrocyte cell line HASTR/ci35. Stable HASTR/ci35 spheroids were successfully formed in MC medium, and laminin deposition was detected inside of the spheroids. Their functional markers were enhanced compared to conventional spheroids formed in U-bottom plates. The inflammatory response was moderately sensitive, and the ability to support neurite growth was confirmed. The HASTR/ci35 spheroid in the MC medium demonstrated the differentiation phenotype and could serve as a potent in vitro model for matured astrocytes.

show abstract

“…Lcn2 is involved in multiple cellular processes, including cellular uptake of iron, apoptosis, suppression of invasiveness and metastasis, and glial activation. It also plays a crucial role in brain injury and recovery after ischemic and hemorrhagic stroke [ 30 , 31 ]. Another study has shown that Lcn2 may exert damaging effects after cerebral ischemia by inducing classical activation of astrocytes [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Ets1 Influences Axonal Growth via Regulation of Lcn2

Gu,

Li,

et al. 2023

Mol Neurobiol

View full text Add to dashboard Cite

Transcription factors are essential for the development and regeneration of the nervous system. The current study investigated key regulatory transcription factors in rat spinal cord development via RNA sequencing. The hub gene Ets1 was highly expressed in the spinal cord during the embryonic period, and then its expression decreased during spinal cord development. Knockdown of Ets1 significantly increased the axonal growth of cultured spinal cord neurons. Luciferase reporter assays and chromatin immunoprecipitation assays indicated that Ets1 could directly bind to the Lcn2 promoter and positively regulate Lcn2 transcription. In conclusion, these findings provide the first direct evidence that Ets1 regulates axon growth by controlling Lcn2 expression, and Ets1 may be a novel therapeutic target for axon regeneration in the central nervous system.

show abstract

Lipocalin-2 and Cerebral Stroke

Cited by 11 publications

References 119 publications

The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment

The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment

Rapid and Stable Formation Method of Human Astrocyte Spheroid in a High Viscous Methylcellulose Medium and Its Functional Advantages

The Transcription Factor Ets1 Influences Axonal Growth via Regulation of Lcn2

Contact Info

Product

Resources

About