Expression of urotensin II is\xa0associated with placental autophagy in patients with severe preeclampsia

Ya-Jing Pan,Lian He,Yang-Yu Zhao,Li-Jie Zhang,Ai-Hua Zhang,Si-Jia Zhou

doi:10.1038/s41371-018-0083-9

Ya-Jing Pan, Lian He + Show 4 more

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https://doi.org/10.1038/s41371-018-0083-9

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Abstract

The aims of this study are to explore the correlation between the expressions of urotensin II (UII) and autophagic markers (LC3 and P62) in patients with severe preeclampsia (SPE). A total of 64 pregnant subjects were recruited, including 29 healthy pregnancies and 35 preeclamptic patients (7 mild preeclamptic (MPE) patients and 28 SPE patients). UII and autophagic markers expression in placenta specimens was investigated by immunohistochemistry (IHC), RT-qPCR, and western blot. IHC analysis manifested that the expressions of UII and autophagic markers were mainly located in the placental cytotrophoblast and syncytiotrophoblast. Western blot and IHC analysis both indicated that the expression of UII was significantly correlated with autophagic marker LC3II (by western blot) or LC3 (by IHC) (r = 0.495, P = 0.010; r = 0.816, P = 0.007). Moreover, SPE group had higher expression of UII and LC3II, lower expression of P62 than that of normal controls. The expression of LC3II was positively related with systolic blood pressure (SBP) and urinary protein level (SBP (r = 0.501, P = 0.003) and urine protein quantitation (r = 0.509, P = 0.022)), whereas P62 had negative correlation with SBP. We first verify that UII has positive correlation with autophagic marker LC3 in placentas of preeclampsia patients; besides, autophagic levels are positively correlated with SBP and urine protein in patients with SPE.

Highlights

Autophagy can be activated by various conditions, such as starvation, hypoxic environment, and high temperatures
Recent studies have uncovered that placental autophagy related to pathogenesis of preeclampsia and autophagic markers were found in cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast [3]
There were significantly higher urinary protein quantitative level and significantly lower gestational weeks in severe preeclampsia (SPE) patients compared to mild preeclampsia (MPE) patients (P < 0.05)

Summary

Introduction

Autophagy can be activated by various conditions, such as starvation, hypoxic environment, and high temperatures. LC3II is a reliable protein marker of autophagosome formation in mammalian cells, and the relative amount of LC3II reflects autophagic activity [1]. P62, called SQSTM1, serving as a link between LC3 and ubiquitinated substrates, and P62-binding protein can be degraded in the autolysosomes, so it can be an index of autophagy [2]. These authors contributed : Ya-Jing Pan, Lian He. Recent studies have uncovered that placental autophagy related to pathogenesis of preeclampsia and autophagic markers were found in cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast [3]. Unfolded or misfolded proteins accumulation in the ER gives rise to stress conditions

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