Downregulation of p53 drives autophagy during human trophoblast differentiation

Gauster, Martin; Maninger, Sabine; Siwetz, Monika; Hiden, Ursula; Desoyé, Gernot; Herse, Florian; Prokesch, Andreas

doi:10.1016/j.placenta.2017.07.226

Cited by 4 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides, p53 is located in the first trimester placental CTBs and combats with LC3B-II levels in STBs. Similar results are also observed in BeWo cell line and placental explants [39]. Bcl-2 is another suppressor of autophagy for its efficacy in binding with Beclin-1.…”

Section: Autophagy-related Genes/molecules In Trophoblastssupporting

confidence: 84%

“…Defects of placentation in high glucose may attribute to ROS-induced autophagy via activating Nrf2 pathway and aberrantly increased expression of differentiationrelated gene expressions (HAND1, MASH2, PL1, MMP12 and IGF2) [104]. During differentiation, overexpression of p53 downregulates the level of LC3B-II, indicating p53 as a negative regulator of autophagy in trophoblast [39]. Interestingly, p53 also serves as a functional link in the crosstalk between autophagy and apoptosis, regulating turnover and homeostasis of trophoblast cells [105].…”

Section: Autophagy Regulates Placentationmentioning

confidence: 99%

See 1 more Smart Citation

Insight of Autophagy in Spontaneous Miscarriage

Qin¹,

Shen²,

Zhou³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.

show abstract

Section: Autophagy-related Genes/molecules In Trophoblastssupporting

confidence: 84%

Section: Autophagy Regulates Placentationmentioning

confidence: 99%

Insight of Autophagy in Spontaneous Miscarriage

Qin¹,

Shen²,

Zhou³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…PLAC8 has been proven to regulate autophagosome‐lysosome fusion 11,12 . Moreover, p53 in the cytoplasm has been previously reported to inhibit autophagy activity 32‐34 . Then, we hypothesized that PLAC8 may regulate autophagy through p53.…”

Section: Discussionmentioning

confidence: 93%

PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells

et al. 2021

View full text Add to dashboard Cite

Autophagy plays an important role in the normal development and function of trophoblast cells and is precisely regulated during pregnancy. Dysregulated autophagy contributes to the abnormal proliferation of trophoblasts, which is closely related to the occurrence of pregnancy‐related diseases. Placenta specific 8 (PLAC8, Onzin) is a multifaceted protein proven to promote autophagy and potentiate various tumor progression. Its role in trophoblasts remains elusive. In our present study, PLAC8 expression was detected in tissues of first‐trimester placentas (n = 5), term placentas (n = 5), choriocarcinoma (n = 5), and placental site trophoblastic tumor (n = 5). PLAC8 expression was increased in gestational neoplasms compared with normal pregnancies. mCherry‐EGFP‐LC3B reporter and transmission electron microscopy confirmed PLAC8 promoted the autophagic flux of human trophoblast cells. Both gain‐of‐function and loss‐of‐function experiments demonstrated PLAC8‐regulated autophagy‐related genes, including ATG5, ATG12, and Beclin‐1. In addition, our data showed that PLAC8 co‐localized with p53 and promoted its degradation, and p53 re‐expression partially abrogated the PLAC8‐induced autophagy activity. Furthermore, the overexpression of PLAC8 promoted cell viability and proliferation, acting as a protective mechanism of trophoblasts against the cytotoxicity of etoposide (VP‐16). Such a phenomenon was effectively abrogated by autophagy inhibitors 3‐methyladenine (3‐MA) and chloroquine (CQ). In conclusion, PLAC8‐induced autophagy to promote the proliferation of trophoblasts. This study provided insights into the mechanism of PLAC8‐induced autophagy in trophoblasts, which is significant for a wide range of gestational diseases and may contribute to developing novel treatment strategies for trophoblastic diseases.

show abstract

“…However, other work suggests TLR4 gene is up‐regulated in the endothelium of the placental villi in placental vascular disease compared with normal pregnancy 47 . These inconsistencies may be explained by low case numbers, differences in gestational age at delivery, and different severity of pathology 48 . Researchers may use different sampling methods resulting in different proportion of cell types in the sample, and select different samples as control group.…”

Section: Discussionmentioning

confidence: 99%

Network analysis reveals important genes in human placenta

Lin

Lai

et al. 2021

J of Obstet and Gynaecol

View full text Add to dashboard Cite

Aim To determine which genes are important in placenta by network analysis. Methods Placenta expressing genes were screened from RNA‐Seq data. Protein–protein interaction data were downloaded from STRING (v11.0) database. Google PageRank (PR) algorithm was used to identify important placental genes from protein interaction network. Six placental disease‐related datasets were downloaded from NCBI GEO database, and the differential expression of the 99 genes was identified. Results We calculated PR for each placenta expressing gene and defined the top 99 genes with high PR as important genes. GAPDH has the highest PR. The 99 genes had different expression pattern in placental cell types. FN1 is up‐regulated in 8 w EVT compared to 8 w CTB and 24 w EVT compared to 8 w EVT. HSPA4 is down‐regulated in 8 w EVT compared to 8 w CTB and 24 w EVT compared to 8 w EVT. MIB2, TLR4, and UBB are consistently changed in preeclampsia (PE). UBB and ACTG1 were identified to be down‐regulated in fetal growth restriction (FGR). SOD1 is down‐regulated in preterm birth placenta. Conclusion Our findings confirmed that the importance of these genes in placenta‐related diseases, and provide new candidates (MIB2, UBB, ACTG1, and SOD1) for placenta‐related disease diagnosis and treatment.

show abstract

Downregulation of p53 drives autophagy during human trophoblast differentiation

Cited by 4 publications

References 21 publications

Insight of Autophagy in Spontaneous Miscarriage

Insight of Autophagy in Spontaneous Miscarriage

PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells

Network analysis reveals important genes in human placenta

Contact Info

Product

Resources

About