Pregnancy Zone Protein (PZP) is significantly upregulated in the decidua of recurrent and spontaneous miscarriage and negatively correlated to Glycodelin A (GdA)

Löb, Sanja; Vattai, Aurelia; Kühn, Christina; Schmoeckel, Elisa; Mahner, Sven; Wöckel, Achim; Kolben, Thomas; Keil, Christiane; Jeschke, Udo; Vilsmaier, Theresa�

doi:10.1016/j.jri.2020.103267

Cited by 16 publications

(13 citation statements)

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“…By exploring the GeneMANIA database, we found at least 14 proteins known to interact with PZP (Figure D). These proteins involve in cell growth (TGFB1 and TGFB2), inflammation (DEFA6 and C2–5), transcription (ZNF135), protein degradation (MMP9, CPAMD8, A2ML1, and A2M), and so forth. − The diverse functions associated with PZP interacting proteins implicate that PZP may be involved in regulating many cellular processes. Taken together, our findings demonstrated that PZP complexes exhibit pro-senescence activity at least in vitro and also hinted that a high level of PZP in the late pregnancy serum is critical for normal fetal development.…”

Section: Resultsmentioning

confidence: 99%

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence

Hu,

Zhang,

Fan

et al. 2023

J. Proteome Res.

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Identification of unique and specific biomarkers to better detect and quantify senescent cells remains challenging. By a global proteomic profiling of senescent human skin BJ fibroblasts induced by ionizing radiation (IR), the cellular level of pregnancy zone protein (PZP), a presumable pan-protease inhibitor never been linked to cellular senescence before, was found to be decreased by more than 10-fold, while the level of PZP in the conditioned medium was increased concomitantly. This observation was confirmed in a variety of senescent cells induced by IR or DNA-damaging drugs, indicating that highlevel secretion of PZP is a novel senescence-associated secretory phenotype. RT-PCR examination verified that the transcription of the PZP gene is enhanced in various cells at senescence or upregulated following DNA damage treatment in a p53-independent manner. Moreover, pretreatment with late pregnancy serum containing a high level of PZP led to inhibition of doxorubicin-induced senescence in A549 cells, and depletion of PZP in the pregnancy serum could enhance such inhibition. Finally, the addition of immuno-precipitated PZP complexes into tissue culture attenuated the growth of A549 cells and promoted the spontaneous senescence. Therefore, we revealed that high-level secretion of PZP is a novel and unique feature associated with DNA damage-induced senescence, and secreted PZP is a positive regulator of cellular senescence, particularly during the late stage of gestation.

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Section: Resultsmentioning

confidence: 99%

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence

Hu,

Zhang,

Fan

et al. 2023

J. Proteome Res.

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“…PZP is also highly expressed in late-pregnancy serum and its upregulation during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation 68 . Furthermore, balanced expression of Glycodelin A (GdA) and its carrier protein PZP in the decidua seems crucial for a successful ongoing pregnancy 70 . Even though we cannot pinpoint putative causal variants, our study provides important additional support for the pathophysiological role of PZP in preeclampsia.…”

Section: Resultsmentioning

confidence: 99%

GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function

Tyrmi

Kaartokallio

Lokki

et al. 2022

Preprint

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Preeclampsia is a vascular pregnancy disorder that affects 3-5% of all pregnancies. Genetic contribution to preeclampsia susceptibility is well established, but the actual risk loci have remained largely unknown. To make further discoveries of the underlying genetic architecture, we performed a new genome-wide association study (GWAS) for maternal preeclampsia and for two other combination phenotypes encompassing maternal preeclampsia and other types of gestational hypertension disorders. We combined the data resources of the Finnish pre-eclampsia cohort ‘FINNPEC’, the Finnish FinnGen project and the Estonian Biobank to obtain cases for the three abovementioned phenotypes. In addition, we performed meta-analyses of the preeclampsia phenotype combining results with the previous largest GWAS results. The controls for each phenotype comprised all parous women in the cohorts not diagnosed with these conditions. In total, we found 18 genome-wide significant associations, of which 12 have not been associated with preeclampsia in any previous maternal GWAS for maternal preeclampsia. Seven of the novel loci were near genes previously associated with blood pressure traits – supporting the concept of pregnancy as a window to future cardiovascular health. The genetic susceptibility to cardiovascular disease may manifest for the first time during pregnancy. Alterations in the integrity of the endothelium or specifically in the glomerular filtration barrier may modify disease susceptibility. Interesting novel associations are in proximity of genes involved in the development of placenta, remodeling of uterine spiral arteries and maintenance of proteostasis in pregnancy serum. Overall, the novel associated genes shed more light on the pathophysiology of preeclampsia.

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“…PZP has been regarded as a pregnancy-associated protein that is remarkably overexpressed in the decidua of recurrent and spontaneous miscarriage ( Lin and Halbert, 1976 ; Lob et al, 2021 ). Previous research suggested that serum PZP levels are notably elevated in patients with ovarian cancer in comparison with those with benign ovarian tumors and in those with cervical or endometrial cancer in comparison with those with benign uterine myomas ( Teng et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Diagnostic Biomarker, PZP, for Detecting Colorectal Cancer in Type 2 Diabetes Mellitus Patients Identified by Serum-Based Mass Spectrometry

Yang

Fang

et al. 2021

Front. Mol. Biosci.

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Background: Growing evidence has confirmed that populations with type 2 diabetes mellitus (T2DM) have an increasing risk of developing colorectal cancer (CRC). Thus, convenient and effective screening strategies for CRC should be developed for the T2DM population to increase the detection rate of CRC.Methods: Twenty serum samples extracted from five healthy participants, five T2DM patients, five CRC patients and five T2DM patients with CRC (T2DM + CRC) were submitted to data-independent acquisition mass spectrometry (DIA-MS) analysis to discover unique differentially altered proteins (DAPs) for CRC in patients with T2DM. Then, the diagnostic value of pregnancy zone protein (PZP) was validated by ELISA analysis in the validated cohort.Results: Based on DIA-MS analysis, we found eight unique proteins specific to T2DM patients with CRC. Among these proteins, four proteins showed different expression between the T2DM + CRC and T2DM groups, and PZP exhibited the largest difference. Next, the diagnostic value of serum PZP was validated by ELISA analysis with an AUC of 0.713. Moreover, the combination of PZP, CA199 and CEA exhibited encouraging diagnostic value, and the AUC reached 0.916.Conclusion: Overall, our current research implied that PZP could be regarded as a newfound serum biomarker for CRC medical diagnosis in T2DM patients.

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Pregnancy Zone Protein (PZP) is significantly upregulated in the decidua of recurrent and spontaneous miscarriage and negatively correlated to Glycodelin A (GdA)

Cited by 16 publications

References 50 publications

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence

High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence

GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function

A Novel Diagnostic Biomarker, PZP, for Detecting Colorectal Cancer in Type 2 Diabetes Mellitus Patients Identified by Serum-Based Mass Spectrometry

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