Detergent-Insoluble Proteome Analysis Revealed Aberrantly Aggregated Proteins in Human Preeclampsia Placentas

Preeclampsia (PE) is a placenta disease,
featured by hypertension,
proteinuria, and other multiorgan dysfunctions, and its etiology is
unclear. We and others have shown that intensive endoplasmic reticulum
(ER) stress and unfolded protein response (UPR) occur in the PE placenta.
In this study, we isolated detergent-insoluble proteins (DIPs) from
human placenta tissues, which were enriched with protein aggregates,
to characterize the placenta UPR in PE. With data-independent acquisition
(DIA) mass spectrometry, we identified 2066 DIPs across all normal
(n = 10) and PE (n = 10) placenta
samples, among which 110 and 108 DIPs were significantly up- and down-regulated
in PE, respectively. Per clustering analysis, differential DIPs could
generally distinguish PE from normal placentas. We verified the MS
quantitation of endoglin and vimentin by immunoblotting. In addition,
we observed that PE placenta tissues have remarkably more endoglin
in the cytoplasm. Furthermore, we found that DIPs were evenly distributed
across different chromosomes and could be enriched in diversified
gene ontology terms, while differential DIPs avoided to distribute
on X-chromosome. Significantly up-regulated DIPs in PE were focused
on the top functions of lipid metabolism, while 23 of these DIPs could
form the top network regulating cellular movement, development, growth,
and proliferation. Our results implicate that human PE placentas have
disease-relevant differential DIPs, which reflect aberrantly aggregated
proteins of placental tissues. The mass spectrometry proteomics data
have been deposited to ProteomeXchange consortium with the data set
identifier PXD006654, and iProX database (accession number: IPX0000948000).