Epicardial Complement C3 Activation in Neonatal Cardiac Regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1252016 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The capacity for some neonatal mammals to regenerate damaged myocardium has a known dependency on immune signaling. By utilizing single cell RNA sequencing of the neonatal mouse heart two days following apical resection or a sham thoracotomy right after birth, we identify complement C3 signaling along an epicardial-to-fetal macrophage axis as playing a strong role in post-injury angiogenesis. Specifically, we identify differences in macrophage populations between surgical conditions, with major expansions in pro-angiogenic signaling fetal liver-derived macrophages post-injury. These results suggest a role for primordial macrophage lineages in the early injury response in the neonatal heart, which may in turn promote better recovery or regeneration.
2025-05-31 | GSE294903 | GEO
Project description:Effects of C3 toxin on RNA profiles in neonatal rat ventricular cardiac myocytes exposed to endothelin-1 (1 h)
2010-05-25 | E-MEXP-1977 | biostudies-arrayexpress
Project description:Host-derived factors are sucked into midgut of mosquitoes during natural malaria transmission, but their influence on malaria transmission is largely unknown. We reported that mouse complement C3 taken into mosquitoes significantly promoted malaria transmission either in laboratory or in field. This effect was attributed to the reduction of microbiota abundance in mosquito midgut by host-derived C3 through direct lyses the predominant symbiont bacteria Elizabethkingia anopheles. Elizabethkingia anopheles symbiont bacteria were demonstrated to be detrimental to malaria sexual stages in mosquitoes. Strikingly, the promoted effect of host C3 on malaria transmission was confirmed by laboratory mosquitoes membrane-feeding on Plasmodium falciparum. Therefore, we reveal a novel strategy of malaria parasite to utilize host complement C3 to promote its transmission, and the administration of C3 inhibitor would provide us a novel strategy to control malaria transmission.
2024-08-01 | GSE271070 | GEO
Project description:Demonstration of renin cleavage of C3. Angiotensinogen and C3 compete for renin-induced complement activation.
2025-04-18 | PXD053116 | Pride
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.
2024-03-13 | GSE199318 | GEO
Project description:Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption the GAPAID consortium examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n=211), with other systemic autoimmune diseases (n=65) and non-autoimmune control subjects (n=149) in two rheumatology tertiary care centers. Standard clinical and laboratory data were collected from all subjects and serum complement levels were determined in SLE patients. The genotype of SNP rs1143679 in the ITGAM gene was also determined. On-chip formation of immune complexes was examined using a functional immunoassay on autoantigen microarray. The amount of antigen-bound IgM, IgG and complement C4 and C3 was quantified on autoantigens comprising nucleic acids, proteins and lipids. Our results show that the relatively high complement consumption of nucleic acids is further increased upon binding of IgM and IgG. This is true even when serum complement levels are decreased due to complement consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, most protein and lipid autoantigens show positive correlation with C4 and C3 levels. Genetic analysis reveals that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) have lower levels of dsDNA specific IgM among SLE patients. Regarding organ involvement we find that besides anti-C1q IgG, low levels of dsDNA specific IgM and low complement C4 binding to C1q are also associated with renal injury. In summary, nucleic acids maintain a skewed complement deposition balance when bound by IgG and IgM, depleting the early classical complement pathway from other physiological processes. Dysfunction of the receptor responsible for complement-mediated apoptotic debris removal promotes the development of autoantibodies targeting nucleic acids. These observations provide serological and genetic evidence for complement-mediated clearance deficiency of apoptotic debris in lupus.
2016-03-07 | GSE69365 | GEO
Project description:The aim of this study was to identify differently expressed genes between C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cells. To elucidate the unresolved mechanism behind the promoting effect of C3156-181 on PNR we cultured primary rat neonatal SCs and treated them for up to 72 h with C3 or C3156-181. We then performed gene expression microarray analysis Results from two loops of two different treatment times are summarized in this study. The samples were taken from two C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cell cultures. Microarrays were hybridized in a loop approach. Results from two loops that map to two different sampling times (loop1: after 12 hours, loop2: after 72) are compared in this study. The data in this file represents loop1. The samples were taken from untreated, C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cells.
2015-07-11 | E-GEOD-70747 | biostudies-arrayexpress
Project description:The aim of this study was to identify differently expressed genes between C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cells. To elucidate the unresolved mechanism behind the promoting effect of C3156-181 on PNR we cultured primary rat neonatal SCs and treated them for up to 72 h with C3 or C3156-181. We then performed gene expression microarray analysis Results from two loops of two different treatment times are summarized in this study. The samples were taken from two C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cell cultures. Microarrays were hybriszed in a loop approach. Results from two loops that map to two different sampling times (loop1: after 12 hours, loop2: after 72) are compared in this study. The data in this file represents loop2. The samples were taken from The samples were taken from untreated, C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cells.
2015-07-11 | E-GEOD-70748 | biostudies-arrayexpress
Project description:Rhabdomyolysis is a severe condition caused by skeletal muscle damage, leading to acute kidney injury (AKI). We demonstrate that complement has a direct pathogenic role in rhabdomyolysis-induced AKI. Deposition of C3d in the tubules of patients and mice correlated with rhabdomyolysis-induced AKI. Moreover, C3-defiient mice with rhabdomyolysis had preserved renal function. Mechanistically, C3-deficiency attenuated strongly inflammatory and apoptotic components of the renal transcriptome, perturbed by rhabdomyolysis. Complement was activated intrarenal by the lectin pathway via collectin-11. It proceeded in a C4-bypass manner and was amplified by heme-activated alternative pathway. Therefore, complement and heme are promising therapeutic targets for rhabdomyolysis-induced AKI.
2020-11-01 | GSE153507 | GEO
Project description:The aim of this study was to identify differently expressed genes between C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cells. To elucidate the unresolved mechanism behind the promoting effect of C3156-181 on PNR we cultured primary rat neonatal SCs and treated them for up to 72 h with C3 or C3156-181. We then performed gene expression microarray analysis Results from two loops of two different treatment times are summarized in this study. The samples were taken from two C3 or C3156-181-peptide treated Isolated primary rat neonatal Schwann Cell cultures. Microarrays were hybriszed in a loop approach.
2015-07-11 | GSE70748 | GEO