HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells

Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore the...

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Published in:	International journal of molecular sciences 2022-05, Vol.23 (10), p.5682
Main Authors:	Li, Sung-Chou, Lan, Kuo-Chung, Hung, Hsuan-Ning, Huang, Wan-Ting, Lai, Yun-Ju, Cheng, Hsin-Hsin, Tsai, Chih-Chang, Huang, Kun-Long, You, Huey-Ling, Hsu, Te-Yao
Format:	Article
Language:	eng
Subjects:	Angiogenesis Assaying biomarker Biomarkers Blood vessels Cesarean Section Cytochemistry Electrophoresis Endothelial cells Endothelial Cells - pathology Female Gel electrophoresis Growth factors Heat shock Heat shock proteins HSP110 Heat-Shock Proteins - metabolism HSPA4 Humans Hypotheses In vivo methods and tests Kinases Morbidity Mortality Muscles Obstetrics Pathogenesis Placenta Placenta - pathology placenta accreta Placenta Accreta - pathology Placenta Accreta - surgery placenta invasion Postpartum period Pregnancy Proteins proteomics Surgery Uterus
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Summary:	Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.
ISSN:	1422-0067 1661-6596 1422-0067