2021
DOI: 10.3389/fcell.2021.652651
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Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction

Abstract: Aberrant ceramide build-up in preeclampsia, a serious disorder of pregnancy, causes exuberant autophagy-mediated trophoblast cell death. The significance of ceramide accumulation for lysosomal biogenesis in preeclampsia is unknown. Here we report that lysosome formation is markedly increased in trophoblast cells of early-onset preeclamptic placentae, in particular in syncytiotrophoblasts. This is accompanied by augmented levels of transcription factor EB (TFEB). In vitro and in vivo experiments demonstrate tha… Show more

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Cited by 14 publications
(20 citation statements)
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“…Ultrathin sections were examined using a Philips CM100 electron microscope (Eindhoven, The Netherlands). Primary lysosomes (electron-dense organelles filled with very tiny granules and usually spheres in three-dimensional shape) and secondary lysosomes (less electron-dense and large heterogeneous more or less spherical organelles) [ 32 ] were identified by two individuals, blinded to the study.…”
Section: Methodsmentioning
confidence: 99%
“…Ultrathin sections were examined using a Philips CM100 electron microscope (Eindhoven, The Netherlands). Primary lysosomes (electron-dense organelles filled with very tiny granules and usually spheres in three-dimensional shape) and secondary lysosomes (less electron-dense and large heterogeneous more or less spherical organelles) [ 32 ] were identified by two individuals, blinded to the study.…”
Section: Methodsmentioning
confidence: 99%
“…6B ). TEM was employed to visualize and quantify primary and secondary lysosomes as previously described [ 20 ] as well as lysosome-mitochondria interactions in isolated pMSCs. While primary lysosome-to-mitochondria interactions were found in pMSCs from early 1 st trimester placentae, numerous secondary lysosome-to-mitochondria interactions (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Specifically, pMSCs isolated from 6 to 8-week placenta and PE placenta were cultured at 3% O 2 , while pMSCs isolated from 10 to 12-week and term placenta were cultured at 8% O 2 . Exosomes were isolated from 24 h conditioned media of term and PE pMSCs as previously reported [ 20 ]. For details on isolation, characterization and uptake of exosomes see Supplementary Methods .…”
Section: Materials/subjects and Methodsmentioning
confidence: 99%
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