Comparison of the transcriptomic profiles of WT and complement C3-deficient mice with rhabdomyolysis-induced acute kidney injury
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ABSTRACT:
PROVIDER: PRJNA642868 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12109400_1.fastq.gz | Fastqsanger.gz | |||
| SRR12109400_2.fastq.gz | Fastqsanger.gz | |||
| SRR12109401_1.fastq.gz | Fastqsanger.gz | |||
| SRR12109401_2.fastq.gz | Fastqsanger.gz | |||
| SRR12109402_1.fastq.gz | Fastqsanger.gz |
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Project description:Perioperative neurocognitive disorder (PNDs) can commonly occur after major surgery in at risk patients and its occurrence increases medical healthcare burdens and even mortality. Accumulating evidence points to neuroinflammation being pivotal to the pathogenesis of these conditions. The complement cascade contributes to neuroinflammatory responses in the central nervous system (CNS) and complement C3 has been implicated in the manifestation of cognitive deficits in several neurological conditions. Neurotoxic reactive astrocytes function differently to their non-activated counterparts and release complement components in response to pathological triggers. We observed previously that surgery induces a rapid rise and then fall in cytokines but a more sustained glial activation response that coincided with postoperative cognitive impairment. In this study, we explored the relationship between the expression of complement C3, glial activation, and cognitive deficits. Using a murine model of surgery, we characterized the transcriptional profiles of hippocampal astrocytes after surgery and examined the effects of C3 suppression on the neuroinflammatory response and cognitive performance. There was a delayed but sustained rise in hippocampal C3 of astrocytic in origin after surgery which corresponded with the onset of cognitive decline. Furthermore, the A1 or the neurotoxic phenotype predominated in this postoperative astrocytic activation, and these cells have a distinct transcriptional profile including C3 upregulation. Suppression of C3 inhibited synaptic phagocytosis by microglia and attenuated postoperative cognitive impairment. Therefore, C3 from reactive astrocytes appear central to the development of cognitive dysfunction associated with postoperative neuroinflammation.
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Project description:Systemic lupus erythematosus is progressive, immune complex-mediated autoimmune disease targeting numerous organs. A central feature of the disease is the development of antibodies against nuclear components, including DNA. Antibodies against double-stranded DNA are so characteristic of this disease that their detection constitutes one of the criteria for diagnosis. We examined the formation of immune complexes on the surface of autoantigen microarrays incubated in the sera of 39 inactive and 22 active lupus patients and of 31 control subjects. Three different kinds of nucleic acids, dsDNA, ssDNA and RNA were used as antigens, along with chromatin (nucleosomal extract) and several other reference molecules. The composition with respect to IgG, IgM and complement components C3 and C4 was determined. We find that while IgM and C4 are physiological components of immune complexes formed from nucleic acids, both IgG and C3 are extremely characteristic of lupus patients. Complement C4 deposition changes were not consistent: these increased on ssDNA and RNA, decreased on chromatin and did not change significantly on dsDNA. The presence of IgG and C3 in the immune complexes formed from different nucleic acids was characteristic for both active and inactive lupus patients. Receiver-operating curve statistics indicate that C3 deposition measurements can improve the efficiency of identification of inactive lupus patients. These observations reveal the complexity of immune profile changes accompanying SLE. C3, IgM, C4 and IgG binding in 92 human serum samples were examined using custom-made protein arrays
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Project description:Systemic lupus erythematosus is progressive, immune complex-mediated autoimmune disease targeting numerous organs. A central feature of the disease is the development of antibodies against nuclear components, including DNA. Antibodies against double-stranded DNA are so characteristic of this disease that their detection constitutes one of the criteria for diagnosis. We examined the formation of immune complexes on the surface of autoantigen microarrays incubated in the sera of 39 inactive and 22 active lupus patients and of 31 control subjects. Three different kinds of nucleic acids, dsDNA, ssDNA and RNA were used as antigens, along with chromatin (nucleosomal extract) and several other reference molecules. The composition with respect to IgG, IgM and complement components C3 and C4 was determined. We find that while IgM and C4 are physiological components of immune complexes formed from nucleic acids, both IgG and C3 are extremely characteristic of lupus patients. Complement C4 deposition changes were not consistent: these increased on ssDNA and RNA, decreased on chromatin and did not change significantly on dsDNA. The presence of IgG and C3 in the immune complexes formed from different nucleic acids was characteristic for both active and inactive lupus patients. Receiver-operating curve statistics indicate that C3 deposition measurements can improve the efficiency of identification of inactive lupus patients. These observations reveal the complexity of immune profile changes accompanying SLE.
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