Activation of AdipoR1 with rCTRP9 Preserves BBB Integrity through the APPL1/AMPK/Nrf2 Signaling Pathway in ICH Mice

Zhao, Wei; Kong, Fanlei; Gong, Xiu; Guo, Zaiyu; Zhao, Limei; Wang, Sa

doi:10.1155/2021/2801263

Cited by 12 publications

(8 citation statements)

References 41 publications

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“…Zhao W et al discovered that APPL1/AMPK/ Nrf2 signaling protected BBB (blood-brain barrier) integrity and enhanced neuronal function in ICH (intracerebral hemorrhage) mice. [29] However, the mechanism of ADIPOR1 in ASD is still unclear, and the relationship between ADIPOR1 and ASD can be explored in the aspect of blood-brain barrier. [30] Earlier research has demonstrated that the expression of genes related to the integrity of blood-brain barrier has changed in the brains of ASD patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of target hub genes and construction of a novel miRNA regulatory network in autism spectrum disorder by integrated analysis

Zhu

Meng

2023

Medicine

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The incidence of autism spectrum disorder (ASD) is increasing year by year in children. The aim of the study was to find possible biomarkers for ASD diagnosis as well as examine MicroRNA (miRNA) signatures and crucial pathways. We conducted a two-stage study to explore potential target genes and functional miRNAs. Peripheral blood samples of children with ASD were enrolled and performed RNA sequencing analysis. The overlapped candidate genes were further screened in combination with differentially expressed genes (DEGs) of GSE77103 datasets. STRING established a protein–protein interaction network comprising DEGs. The hub genes were filtered out using the CytoHubba. Then, we set up a miRNA-mRNA regulatory network. Correlational analyses between hub genes and immune cells associated with ASD were carried out using the CIBERSORT software to assess the diversity of immune cell types in ASD. RNA-sequencing analysis was used to confirm the differential expression of 3 hub genes. Briefly, after blood samples were sequenced interrogating 867 differential genes in our internal screening dataset. After screening GEO databases, 551 DEGs obtained from GSE77103. Fourteen common genes were overlapped through DEGs of GEO datasets and internal screening dataset. Among protein–protein interaction network, 10 hub genes with high degree algorithm were screened out and 3 hub genes of them – ADIPOR1, LGALS3, and GZMB – that were thought to be most associated with the emergence of ASD. Then, we developed a network of miRNA-mRNA regulatory interactions by screening miRNAs (such as hsa-miR-20b-5p, hsa-miR-17-5p, and hsa-miR-216b-5p) that were closely associated to 3 hub genes. Additionally, we discovered 18 different immune cell types associated with ASD using the CIBERSORT algorithm, and we discovered that mononuclear macrophages differed considerably between the 2 groups. Overall, 3 hub genes (ADIPOR1, LGALS3, and GZMB) and 15 candidates miRNAs-target 3 genes regulatory pathways representing potentially novel biomarkers of ASD diseases were revealed. These findings could enhance our knowledge of ASD and offer possible therapeutic targets of ASD patients in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of target hub genes and construction of a novel miRNA regulatory network in autism spectrum disorder by integrated analysis

Zhu

Meng

2023

Medicine

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“…Recent studies have shown that AdipoR1 could maintain the integrity of the blood-brain barrier through the APPL1/AMPK/Nrf2 signaling pathway [ 36 ]. And Nrf2 exerts its antioxidant role in cellular protection by regulating xCT expression [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway

Feng

Liu

Gan

et al. 2022

Oxidative Medicine and Cellular Longevity

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Radiotherapy has been used for decades in the treatment of liver cancer. We previously found that adiponectin receptor (AdipoR1) is a prognostic biomarker for hepatoma carcinoma (HCC) after stereotactic body radiation therapy (SBRT) and blocking AdipoR1 enhances radiation sensitivity in hepatoma carcinoma cells. In the current study, we aimed to elucidate the roles of AdipoR1 in ionizing radiation- (IR-) induced radiosensitivity by activating ferroptosis pathway in HCC cells. We found that IR upregulated the expression of AdipoR1 and furthermore promoted the protein stability of transcription factor Nrf2, Nrf2 binded to the xCT promoter and increased xCT transcription and expression, and this directly contributed to the protective function in the early stage of radiation in HCC cells. AdipoR1 knockdown significantly inhibited expression of Nrf2 and xCT and, furthermore, increased both IR- and erastin-induced ferroptosis, which could be abolished by the rescue of Nrf2 and xCT. For the first time, we found that radiation-induced ferroptosis was mediated by AdipoR1-Nrf2-xCT pathway in HCC cells. These results provide new insights to the development and application of novel therapeutic strategies for hepatoma carcinoma.

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“…Administration of CTRP9 treatment improved AdipoR1 and p-AMPK protein expression levels and decreased the protein expression levels of inflammatory cytokines and phosphorylated NFκB (P-NFκB), attenuating neuroinflammation via AdipoR1/AMPK/NFκB signaling pathway (Zhao et al, 2018 ). Activated AdipoR1 by CTRP9 treatment attenuated neuropathological deficits and improved BBB dysfunction by activating the APPL1/AMPK/Nrf2 signal axis in a collagenase-induced ICH mouse model (Xu et al, 2018 ; Zhao et al, 2021 ). This evidence suggested that CTRP9 could be recognized as an encouraging therapy to ameliorate BBB dysfunction in ICH patients.…”

Section: Potential Therapeutic Targets and Strategies Of Microglia-in...mentioning

confidence: 99%

Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention

Yang

Fan

Mazhar

et al. 2022

Front. Mol. Neurosci.

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Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in neurological diseases, including intracerebral hemorrhage (ICH). Microglia are activated to acquire either pro-inflammatory or anti-inflammatory phenotypes. After the onset of ICH, pro-inflammatory mediators produced by microglia at the early stages serve as a crucial character in neuroinflammation. Conversely, switching the microglial shift to an anti-inflammatory phenotype could alleviate inflammatory response and incite recovery. This review will elucidate the dynamic profiles of microglia phenotypes and their available shift following ICH. This study can facilitate an understanding of the self-regulatory functions of the immune system involving the shift of microglia phenotypes in ICH. Moreover, suggestions for future preclinical and clinical research and potential intervention strategies are discussed.

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Activation of AdipoR1 with rCTRP9 Preserves BBB Integrity through the APPL1/AMPK/Nrf2 Signaling Pathway in ICH Mice

Cited by 12 publications

References 41 publications

Identification of target hub genes and construction of a novel miRNA regulatory network in autism spectrum disorder by integrated analysis

Identification of target hub genes and construction of a novel miRNA regulatory network in autism spectrum disorder by integrated analysis

AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway

Neuroinflammation of microglia polarization in intracerebral hemorrhage and its potential targets for intervention

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