SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway

Long, Yan; Zeng, Shanshui; Gao, Fei; Liu, Fei; Zhang, Yonggang; Cheng, Zhiyong; Zhu, Chunyan; Zhao, Xin; Han, Mengru; Gan, Qiangsheng; Ye, Weitao; Zeng, Fangling; Song, Chunlin; Jiang, Min; Lash, Gendie E.; Yang, Hongling

doi:10.1016/j.trsl.2022.06.011

Cited by 2 publications

(6 citation statements)

References 45 publications

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“…We similarly noticed elevated SERPINA5 expression in the liver and kidneys of PE rats but to different degrees. Our earlier research has shown that during severe inflammation, HTR-8/SVneo cells can express SERPINA5 [16]. The increased expression of SERPINA5 in response to the pathophysiological changes in PE is further supported by our study.…”

Section: Discussionsupporting

confidence: 88%

“…Previous studies have demonstrated a correlation between increased SERPINA5 levels and decreased trophoblast cell invasiveness. Additionally, overexpressing SERPINA5 during gestation may cause clinical features in rats that resemble PE [15,16]. The overexpression of placenta-derived SERPINA5 was further demonstrated in this study to cause the dysregulation of blood coagulation, which was linked to anomalous placental development and pathological alterations in the kidneys.…”

Section: Discussionsupporting

confidence: 57%

“…We previously found that high levels of SERPINA5 induced PE-like features in rats [16], which could explain why SERPINA5 overexpression exacerbated PE features in L-NAMEinduced model rats. Moreover, we detected pathological changes in rat kidneys following SERPINA5 overexpression, akin to previously established PE models [33,34].…”

Section: Discussionmentioning

confidence: 94%

“…Our previous research suggested that serum levels of SERPINA5 were elevated fivefold before the onset of PE, potentially promoting PE progression by inhibiting uPA/uPAR signaling and thus suppressing EVT invasion [15,16]. SERPINA5, a protein C inhibitor (PCI), is a serine protease inhibitor.…”

Section: Introductionmentioning

confidence: 99%

“…It plays a critical role in limiting the activity of the anticoagulant protein C. SERPINA5 is involved in many biological processes, including inflammation, coagulation, and responses to elevated platelet cytoplasmic Ca 2+ . An in vivo study demonstrated that SERPINA5 overexpression could induce PE-like features in multiple organs in rats [16]. However, the organ or tissue which secretes SERPINA5 protein during PE pregnancy remains uncertain, and whether it could serve as a potential intervention target.…”

Section: Introductionmentioning

confidence: 99%

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Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression

Zeng,

Liu,

Yin

et al. 2023

Biomolecules

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Pre-eclampsia (PE) is a severe pregnancy disorder that poses a significant health risk to both mother and fetus, with no preventive or therapeutic measures. Our previous research suggested an association between elevated SERPINA5 levels and PE features. This study investigated whether SERPINA5 could be a potential therapeutic target for PE. We established PE-like features in pregnant rats using L-NAME (75 mg/kg/d) treatment. Adenoviruses carrying overexpressed or suppressed SERPINA5 genes were intravenously injected into these PE rats on the fifth and seventh days of pregnancy. We evaluated the rats’ systolic blood pressure, urine protein concentration, and placental and fetal metrics and histology. Placental gene expression following SERPINA5 overexpression was evaluated using mRNA sequencing. The L-NAME-induced PE rat model observed a significant increase in placental and peripheral SERPINA5 levels. The overexpression of SERPINA5 exacerbated L-NAME-induced hypertension and proteinuria in pregnant rats. A histology examination revealed a smaller placental junctional zone in L-NAME + overexpressing rats. Placental gene expression analysis in the L-NAME + overexpressing group indicated increased coagulation activation. L-NAME-induced hypertension and proteinuria were mitigated when SERPINA5 expression was suppressed. Additionally, placental development was improved in the SERPINA5-suppressed group. Our findings suggested that SERPINA5 may worsen L-NAME-induced PE-like features by promoting the activation of the coagulation cascade. Therefore, reducing SERPINA5 expression could potentially serve as a therapeutic strategy for PE.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression

Zeng,

Liu,

Yin

et al. 2023

Biomolecules

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Investigating the Role of Urokinase in Cancer Metastasis: A Review

Datta

2023

Preprint

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The greatest cause of cancer-related mortality is cancer metastasis, which is the spread of cancer cells from the original tumour to distant areas. Urokinase (uPA) is one of the important proteases involved in this process. By encouraging cell migration, invasion, and angiogenesis, uPA plays a critical part in the spread of cancer. Numerous cancers have an overexpressed uPA system, which is linked to a poor prognosis and a higher chance of metastasis. The project focuses on the state of the science around uPA inhibitors as a possible therapeutic for preventing or treating cancer metastasis. Different kinds of uPA inhibitors, including as monoclonal antibodies, small molecule inhibitors, and plasminogen activator inhibitors (PAIs), have been created and have showed promise in preclinical investigations. To prove their effectiveness in treating cancer patients, more study is necessary. A promising strategy for preventing or treating cancer metastasis involves targeting the uPA system with specific inhibitors or through techniques like gene therapy, anti-uPA/uPAR antibodies, uPA-targeted nanoparticles, and dual inhibitors that target multiple proteases involved in cancer metastasis. uPA inhibitors have also been researched as potential indicators for estimating the likelihood of cancer spread.

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SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway

Cited by 2 publications

References 45 publications

Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression

Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression

Investigating the Role of Urokinase in Cancer Metastasis: A Review

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