Publication:
Placental malaria is associated with a TLR–Endothelin-3–oxidative damage response in 1 human placenta tissues

Simple item page
dc.contributor.authorChenge, Samuel
dc.contributor.authorMbalitsi, Melvin
dc.contributor.authorNgure, Harrison
dc.contributor.authorObimbo, Moses
dc.contributor.authorSingoei, Mercy
dc.contributor.authorKangogo, Mourine
dc.contributor.authorKanoi1, Bernard N
dc.contributor.authorGitaka, Jesse
dc.contributor.authorKobia, Francis M.
dc.date.accessioned2024-06-03T08:49:19Z
dc.date.available2024-06-03T08:49:19Z
dc.date.issued2024-04-20
dc.description.abstractPlacental malaria, which is mainly caused by the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is an important driver of poor pregnancy outcomes, including fetal growth restriction, preterm birth, and stillbirth. However, the mechanisms underlying its adverse outcomes are unclear. Mouse models have previously shown that placental malaria (PM) triggers a proinflammatory response in the placenta, which is accompanied by a fetal Toll-like receptor (TLR)4-mediated innate immune response associated with improved fetal outcomes. Here, we used hematoxylin and eosin staining to identify PM-positive and negative samples in our biobank of placentas donated by women living in a malaria-endemic region of Kenya and assessed the impact of PM on the expression of TLRs, Endothelins, and oxidative damage. RT-qPCR analysis revealed that PM was associated with an upregulation of TLR4, TLR7, and Endothelin-3. Moreover, immunohistochemistry showed that PM was associated with elevated expression levels of the oxidative DNA damage marker, 8-hydroxy-2’-deoxyguanosine, while RT-qPCR revealed that this was accompanied by an upregulation of p21, an inhibitor of cell cycle progression and marker of cellular response to DNA damage. These findings allude to a novel mechanism of PM pathogenesis driven by a TLR–Endothelin-3–oxidative DNA damage signaling axis.
dc.identifier.urihttps://doi.org/10.1101/2024.04.17.589949
dc.identifier.urihttps://erepository.mku.ac.ke/handle/123456789/5807
dc.language.isoen
dc.publishermedRxiv and bioRxiv
dc.subjectPlacental malaria
dc.subjectplacenta tissues
dc.subjectTLR–Endothelin-3–oxidative
dc.titlePlacental malaria is associated with a TLR–Endothelin-3–oxidative damage response in 1 human placenta tissues
dc.typeArticle
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2024.04.17.589949v1.full.pdf
Size:
912.92 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Clinical Medicine