Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus
Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunc...
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MDPI AG
2021-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/2/251 |
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| author | Dumitru Iacobas Jing Wen Sanda Iacobas Noa Schwartz Chaim Putterman |
| author_facet | Dumitru Iacobas Jing Wen Sanda Iacobas Noa Schwartz Chaim Putterman |
| author_sort | Dumitru Iacobas |
| collection | DOAJ |
| description | Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/<i>lpr</i> (that manifest lupus-like phenotype) and MRL/<i>lpr</i>-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL/<i>lpr</i> lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models. |
| first_indexed | 2024-03-09T04:52:39Z |
| format | Article |
| id | doaj.art-1fdd1b8e0bec4b8ab7f4289e5264c784 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T04:52:39Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-1fdd1b8e0bec4b8ab7f4289e5264c7842023-12-03T13:08:39ZengMDPI AGGenes2073-44252021-02-0112225110.3390/genes12020251Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus ErythematosusDumitru Iacobas0Jing Wen1Sanda Iacobas2Noa Schwartz3Chaim Putterman4Center for Computational Systems Biology, Personalized Genomics Laboratory, Roy G. Perry College of Engineering, Prairie View A & M University, Prairie View, TX 77446, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Pathology, New York Medical College, Valhalla, NY 10595, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USACognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/<i>lpr</i> (that manifest lupus-like phenotype) and MRL/<i>lpr</i>-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL/<i>lpr</i> lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.https://www.mdpi.com/2073-4425/12/2/251neuropsychiatric lupusTWEAKTnfsf12Fn14Tnfrsf12aAkt2 |
| spellingShingle | Dumitru Iacobas Jing Wen Sanda Iacobas Noa Schwartz Chaim Putterman Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus Genes neuropsychiatric lupus TWEAK Tnfsf12 Fn14 Tnfrsf12a Akt2 |
| title | Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus |
| title_full | Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus |
| title_fullStr | Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus |
| title_full_unstemmed | Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus |
| title_short | Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus |
| title_sort | remodeling of neurotransmission chemokine and pi3k akt signaling genomic fabrics in neuropsychiatric systemic lupus erythematosus |
| topic | neuropsychiatric lupus TWEAK Tnfsf12 Fn14 Tnfrsf12a Akt2 |
| url | https://www.mdpi.com/2073-4425/12/2/251 |
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