PZP, or Pregnancy Zone Protein, is a multifunctional protein. It belongs to the proteinase inhibitor I39 (α -2 -macroglobulin) family [4]. Initially identified as a protease inhibitor, current evidence suggests it may also function as a modulator of T -helper cells and/or extracellular chaperone. PZP is elevated in normal pregnancy and numerous inflammatory states, and is implicated in maintaining proteostasis in pregnancy serum, with its reduced levels associated with preeclampsia, a major cause of maternal and foetal morbidity and mortality [1,2]. It also has a role in animals with invasive placenta as it accumulates at the maternal-foetal interface during the second trimester in humans [3].

In hepatocellular carcinoma (HCC), the gene encoding PZP is hypermethylated and expressed at low levels. Functionally, PZP markedly inhibits the proliferation, invasion, and migration of HCC cells, suggesting its potential as a novel therapeutic target [4]. In preeclampsia and HELLP syndrome, PZP expression is significantly downregulated in the syncytiotrophoblast and extravillous trophoblast of the placenta, indicating its involvement in placental dysfunction development [5].

In summary, PZP is important in pregnancy-related physiological processes and shows potential associations with diseases like preeclampsia and HCC. Its role in maintaining pregnancy-related proteostasis and its influence on cell proliferation and invasion in cancer highlight its significance. Understanding PZP through study models could offer insights into the pathogenesis of these diseases and potentially lead to new treatment strategies.

References:

1. Wyatt, Amy R, Cater, Jordan H, Ranson, Marie. 2016. PZP and PAI-2: Structurally-diverse, functionally similar pregnancy proteins? In The international journal of biochemistry & cell biology, 79, 113-117. doi:10.1016/j.biocel.2016.08.018. https://pubmed.ncbi.nlm.nih.gov/27554634/

2. Tyrmi, Jaakko S, Kaartokallio, Tea, Lokki, A Inkeri, Kere, Juha, Laivuori, Hannele. . Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy. In JAMA cardiology, 8, 674-683. doi:10.1001/jamacardio.2023.1312. https://pubmed.ncbi.nlm.nih.gov/37285119/

3. Kashiwagi, Hirofumi, Ishimoto, Hitoshi, Izumi, Sun-Ichiro, Mikami, Mikio, Kametani, Yoshie. 2020. Human PZP and common marmoset A2ML1 as pregnancy related proteins. In Scientific reports, 10, 5088. doi:10.1038/s41598-020-61714-8. https://pubmed.ncbi.nlm.nih.gov/32198464/

4. Wu, Minhua, Lan, Hui, Ye, Zhongwei, Wang, Yonghui. 2021. Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration. In FEBS open bio, 11, 826-832. doi:10.1002/2211-5463.13093. https://pubmed.ncbi.nlm.nih.gov/33471436/

5. Löb, Sanja, Vattai, Aurelia, Kuhn, Christina, Mahner, Sven, Jeschke, Udo. 2022. The Pregnancy Zone Protein (PZP) is significantly downregulated in the placenta of preeclampsia and HELLP syndrome patients. In Journal of reproductive immunology, 153, 103663. doi:10.1016/j.jri.2022.103663. https://pubmed.ncbi.nlm.nih.gov/35843132/