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Complement - U.S. Department of Veterans Affairs

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Last Updated: 03 September 2022

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Endothelial-specific loss of Krüppel-Like Factor 4 triggers complement-mediated endothelial injury.

The most prominent sign of kidney microvascular endothelial injury is thrombosis in the kidney. Despite the source of the inciting event, the various clinical manifestations of kidney TMA also contribute to endothelial cell transcript expression and complement activation. Interestingly, complement activation in Klf4u0394EC mice was followed by decreased expression of a key KLF4 transcriptional target and membrane bound complement regulatory gene, Cd55. We investigated the CD55 progenitor's chromatin immunoprecipitation enrichment study, finding KLF4 binding sites upstream from the CD55 transcription start site to determine a potential mechanism by which KLF4 might control CD55 expression. Patients with TMA were reduced in patients with TMA, relative to control biopsies of the unaffected pole of patient kidneys removed due to kidney cancer, using patient-derived kidney biopsy results.

Source link: https://doi.org/10.1016/j.kint.2022.03.025


Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study.

Following traumatic brain injury, initiation of the complement system promotes neuroinflammation and brain injury early and chronically. Moreover, complement therapeutic studies have concentrated on a small number of histopathologic studies, which, although useful, do not investigate the effect of complement inhibition on neuroprotection and inflammation in a systematic manner. We simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI using high-throughput gene expression technologies. Moreover, TBI upregulated gene expression in both complement activation and effector pathways, with an early emphasis on classical pathway genes and continued upregulation of C2, C3 and C4 expression two years post-injury. Our results show that complement gene expression in the human and elderly brain as well as general and chronic dysregulation of the complement system after TBI, leading to widespread and persistent dysregulation of the complement system after TBI, which increases the possibility that the complement system is a promising target for TBI therapy.

Source link: https://doi.org/10.1186/s40478-021-01226-2


Complement mediates neuroinflammation and cognitive decline at extended chronic time points after traumatic brain injury.

Traumatic brain injury can cause progressive cognitive decline years after the initial insult, which is why there is currently no pharmacological cure. However, mice receiving continuous CR2Crry therapy demonstrated improved spatial learning and memory as compared to mice receiving only 3 doses and mice receiving vehicle control. In the continuing CR2Crry treatment program, there were still complement activation in brain sections six months after injury, with reduced complement activation and C3 deposition. In mice that were not consistently treated with CR2Crry, there was also elevated astrocytosis in the contralateral hippocampus of vehicle-treated vs. nafve mice, which was reduced in mice treated with CR2Crry. This research finds that complement mediated neuroinflammation at longer time points after TBI, as well as an extension of the potential treatment window for complement inhibition, which has previously been shown to improve outcomes following murine TBI.

Source link: https://doi.org/10.1186/s40478-021-01179-6

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions