Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization

Lee, So Young; Lee, Yun Young; Choi, Joong Sub; Kim, Kyeong Soo; Min, Do Sik; Park, Shin Young; Han, Joong‐Soo

doi:10.1096/fj.202001212r

Cited by 3 publications

(1 citation statement)

References 60 publications

(166 reference statements)

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“…RAS-associated protein 1 (RAP1), a member of the small G protein family of RAS, influences the tumor development and progression by engaging in various biological processes such as cell proliferation, invasion, migration, and apoptosis imbalance [ 42 , 43 ]. A recent study showed that PP2Ac nitration during cAMP-induced decidualization of hESCs was induced through the Epac1-Rap1-PLC ε -CaMKII-HDAC5-iNOS signaling pathway [ 44 ]. It has been found that RAP1A and EPAC1 were highly expressed in ovarian endometriosis and their expressions were positively correlated, speculating that RAP1A and EPAC1 may cooperate with each other to participate in the occurrence and development of EMs and in the regulation of dysmenorrhea.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression and Bioinformatics Analysis of tRF/tiRNA in Endometriosis Patients

Wangshu¹,

Li²,

Cao³

et al. 2022

BioMed Research International

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Background. Endometriosis (EMs) is a benign chronic condition that tends to recur in women of childbearing age, with an incidence of approximately 10%. It is a multifactorial disease for which the pathogenesis is currently unclear. This study is aimed at investigating the expression and clinical significance of tRNA-derived small RNA (tsRNA), a novel noncoding small RNA with potential regulatory functions, in endometriosis. Methods. The tRF/tiRNA expression profiles in endometrial tissues from three pairs of endometriosis patients and controls were detected by tRF&tiRNA PCR microarray technology and then verified by quantitative real-time polymerase chain reaction (qPCR). The target genes and target sites of TRF396, tiRNA-5030-GlnTTG-3, TRF308, and TRF320 were predicted by miRanda, and the network diagram of their interaction with miRNA was drawn. The impact of tRNA-derived fragments on the pathogenesis of endometriosis was analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results. Two upregulated and 19 downregulated tRNA-derived fragments were identified. The qRT-PCR results of 2 upregulated and 2 downregulated RNA-derived fragments were consistent with the RNA Seq data. The OR2B4 gene related to TRF396, the DGAT1 gene related to tiRNA-5030-GlnTTG-3, the KLF16 gene of TRF308, and the RNF213 gene of TRF320 had significant correlations. Gene Ontology and pathway analysis showed that the target genes of TRF396 and tiRNA-5030-GlnTTG-3 were mainly involved in the intrinsic components of the membrane and the overall composition of the membrane in cell components; molecular functions mainly involve olfactory conduction and G protein-coupled receptor activity. In the biological process, it was mainly involved in the detection of sensory stimuli. The target genes of TRF308 and TRF320 were mainly involved in the intracellular part; molecular functions are mainly related to DNA binding transcription factor activity and protein binding and mainly related to biological regulation of biological processes. Pathway analysis showed that the RAP1 signaling pathway and the AXON GUIDANCE signaling pathway may participate in the progression of endometriosis. Conclusion. The differential expression of tRF/tiRNA in endometriosis may be related to the pathogenesis of endometriosis. Furthermore, tRF/tiRNA may be a biomarker for the diagnosis and treatment of EMs in the future.

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Section: Discussionmentioning

confidence: 99%

Differential Expression and Bioinformatics Analysis of tRF/tiRNA in Endometriosis Patients

Wangshu¹,

Li²,

Cao³

et al. 2022

BioMed Research International

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Research advances in endometriosis-related signaling pathways: A review

Zhang

Tong

et al. 2023

Biomedicine & Pharmacotherapy

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Bone Marrow Mesenchymal Stem Cells (BMSCs) Enhance the In Vitro Activities of Endometrial Cells via Strengthening the Phosphorylation and Activation of Phosphoinositide 3-Kinase (PI3K)

Zeng

Zhu

Wen

et al. 2023

j biomater tissue eng

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Mancozeb (ethylene bis-dithiocarbamate) is an organometallic fungicide and is widely used in agriculture and is related to women’s spontaneous abortion and menstrual abnormalities. Bone marrow mesenchymal stem cells (BMSCs) can impede endometrial fibrosis via suppressing PI3K pathway, but its effect on the activity of endometrial cells induced by mancozeb/EDU is unclear. This study intends to explore the protective effects of co-culture with BMSCs on endometrial cells after mancozeb/EDU treatment. Endometrial cells were randomized into control group, mancozeb/EDU group (mancozeb/EDU treatment), BMSCs group (cells were co-cultured with BMSCs after mancozeb/EDU treatment), and inhibitor group (treated with PI3K-Akt-mTOR inhibitor) followed by analysis of the expression of PI3K-Akt-mTOR pathway-related proteins, cell viability by MTT and cell invasion and migration by Transwell and scratch test. Mancozeb/EDU treatment significantly inhibited PI3K-Akt-mTOR signals and cell proliferation, increased apoptosis and decreased cell invasion and migration, which were all reversed by co-culture with BMSCs. Additionally, the co-culture with BMSCs modulated the In Vitro viability of endometrial cells by influencing PI3K-Akt-mTOR signal transduction pathway, which can be inverted by PI3K-Akt-mTOR pathway-specific antagonists. In conclusion, BMSCs exerted a protective effect on the In Vitro viability of endometrial cells by manipulating the PI3K/Akt/mTOR signal transduction, which helped to protect endometrial cells from damage caused by mancozeb/ETU treatment.

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Nitration of protein phosphatase 2A increases via Epac1/PLCε/CaMKII/HDAC5/iNOS cascade in human endometrial stromal cell decidualization

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 3 publications

References 60 publications

Differential Expression and Bioinformatics Analysis of tRF/tiRNA in Endometriosis Patients

Differential Expression and Bioinformatics Analysis of tRF/tiRNA in Endometriosis Patients

Research advances in endometriosis-related signaling pathways: A review

Bone Marrow Mesenchymal Stem Cells (BMSCs) Enhance the In Vitro Activities of Endometrial Cells via Strengthening the Phosphorylation and Activation of Phosphoinositide 3-Kinase (PI3K)

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