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Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific complication characterized by pruritus without skin damage and jaundice. The poor perinatal outcomes include fetal distress, preterm birth, and unexpected intrauterine death. However, the mechanism of ICP leading to poor...

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Autores principales: Fang, Dajun, Fang, Yan, Zhang, Weiqiang, Xiang, Yun, Cheng, Xi, Liang, Mingfeng, Xia, Huimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354660/
https://www.ncbi.nlm.nih.gov/pubmed/35938169
http://dx.doi.org/10.3389/fcell.2022.854425
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author Fang, Dajun
Fang, Yan
Zhang, Weiqiang
Xiang, Yun
Cheng, Xi
Liang, Mingfeng
Xia, Huimin
author_facet Fang, Dajun
Fang, Yan
Zhang, Weiqiang
Xiang, Yun
Cheng, Xi
Liang, Mingfeng
Xia, Huimin
author_sort Fang, Dajun
collection PubMed
description Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific complication characterized by pruritus without skin damage and jaundice. The poor perinatal outcomes include fetal distress, preterm birth, and unexpected intrauterine death. However, the mechanism of ICP leading to poor prognosis is still unclear. Methods: We analyzed 10 ICP and 10 normal placental specimens through quantitative proteomics of data-independent acquisition (DIA) to screen and identify differentially expressed proteins. GO, KEGG, COG/KOG, StringDB, InterProScan, Metascape, BioGPS, and NetworkAnalyst databases were used in this study. PITA, miRanda, TargetScan, starBase, and LncBase Predicted v.2 were used for constructing a competing endogenous RNA (ceRNA) network. Cytoscape was used for drawing regulatory networks, and cytoHubba was used for screening core nodes. The ICP rat models were used to validate the pathological mechanism. Results: GO, KEGG, and COG/KOG functional enrichment analysis results showed the differentially expressed proteins participated in autophagy, autophagosome formation, cofactor binding, JAK-STAT signaling pathway, and coenzyme transport and metabolism. DisGeNET analysis showed that these differentially expressed proteins were associated with red blood cell disorder and slow progression. We further analyzed first 12 proteins in the upregulated and downregulated differentially expressed proteins and incorporated clinicopathologic parameters. Our results showed HBG1, SPI1, HBG2, HBE1, FOXK1, KRT72, SLC13A3, MBD2, SP9, GPLD1, MYH7, and BLOC1S1 were associated with ICP development. ceRNA network analysis showed that MBD2, SPI1, FOXK1, and SLC13A3 were regulated by multiple miRNAs and lncRNAs. Conclusion: ICP was associated with autophagy. The ceRNA network of MBD2, SPI1, FOXK1, and SLC13A3 was involved in ICP progression, and these core proteins might be potential target.
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spelling pubmed-93546602022-08-06 Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy Fang, Dajun Fang, Yan Zhang, Weiqiang Xiang, Yun Cheng, Xi Liang, Mingfeng Xia, Huimin Front Cell Dev Biol Cell and Developmental Biology Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific complication characterized by pruritus without skin damage and jaundice. The poor perinatal outcomes include fetal distress, preterm birth, and unexpected intrauterine death. However, the mechanism of ICP leading to poor prognosis is still unclear. Methods: We analyzed 10 ICP and 10 normal placental specimens through quantitative proteomics of data-independent acquisition (DIA) to screen and identify differentially expressed proteins. GO, KEGG, COG/KOG, StringDB, InterProScan, Metascape, BioGPS, and NetworkAnalyst databases were used in this study. PITA, miRanda, TargetScan, starBase, and LncBase Predicted v.2 were used for constructing a competing endogenous RNA (ceRNA) network. Cytoscape was used for drawing regulatory networks, and cytoHubba was used for screening core nodes. The ICP rat models were used to validate the pathological mechanism. Results: GO, KEGG, and COG/KOG functional enrichment analysis results showed the differentially expressed proteins participated in autophagy, autophagosome formation, cofactor binding, JAK-STAT signaling pathway, and coenzyme transport and metabolism. DisGeNET analysis showed that these differentially expressed proteins were associated with red blood cell disorder and slow progression. We further analyzed first 12 proteins in the upregulated and downregulated differentially expressed proteins and incorporated clinicopathologic parameters. Our results showed HBG1, SPI1, HBG2, HBE1, FOXK1, KRT72, SLC13A3, MBD2, SP9, GPLD1, MYH7, and BLOC1S1 were associated with ICP development. ceRNA network analysis showed that MBD2, SPI1, FOXK1, and SLC13A3 were regulated by multiple miRNAs and lncRNAs. Conclusion: ICP was associated with autophagy. The ceRNA network of MBD2, SPI1, FOXK1, and SLC13A3 was involved in ICP progression, and these core proteins might be potential target. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9354660/ /pubmed/35938169 http://dx.doi.org/10.3389/fcell.2022.854425 Text en Copyright © 2022 Fang, Fang, Zhang, Xiang, Cheng, Liang and Xia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Fang, Dajun
Fang, Yan
Zhang, Weiqiang
Xiang, Yun
Cheng, Xi
Liang, Mingfeng
Xia, Huimin
Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title_full Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title_fullStr Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title_full_unstemmed Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title_short Comprehensive Analysis of Quantitative Proteomics With DIA Mass Spectrometry and ceRNA Network in Intrahepatic Cholestasis of Pregnancy
title_sort comprehensive analysis of quantitative proteomics with dia mass spectrometry and cerna network in intrahepatic cholestasis of pregnancy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354660/
https://www.ncbi.nlm.nih.gov/pubmed/35938169
http://dx.doi.org/10.3389/fcell.2022.854425
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