Expression Patterns of Two Serine Protease HtrA1 Forms in Human Placentas Complicated by Preeclampsia with and without Intrauterine Growth Restriction

Lorenzi, Teresa; Marzioni, Daniela; Giannubilo, Stefano Raffaele; Quaranta, Alexia; Crescimanno, Caterina; Luca, Antonio De; Baldi, Alfonso; Todros, Tullia; Tranquilli, Andrea Luigi; Castellucci, Mario

doi:10.1016/j.placenta.2008.10.016

Cited by 46 publications

(40 citation statements)

References 33 publications

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“…The mRNA level of this gene was elevated approximately 4-fold in placentae from women with preeclampsia when compared to normal controls. This is in accordance with a recently published study which exhibited similar results for HTRA1, a member of the family of HTRA proteins, which is a secreted multidomain protein with serine protease activity and which is involved in the physiological development of many organs as well as in the development of several pathologies [27,28]. …”

Section: Discussionsupporting

confidence: 93%

Microarray Screening for Novel Preeclampsia Biomarker Candidates

Lapaire¹,

Grill²,

Lalevée³

et al. 2012

Fetal Diagn Ther

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Introduction: Our aim was to identify novel biomarker candidates for the near-term prediction of preeclampsia in a homogenous collective. In this study, we screened at the genome-wide level for gene expression in placental villous tissue from patients with severe preeclampsia in comparison to normal healthy pregnancies. Material and Methods: Total RNA was extracted from placental villous tissue from 9 preeclamptic patients and 7 normotensive controls after scheduled cesarean sections. After sample pooling, gene expression analysis was performed using six Affymetrix Human Gene 1.0 ST arrays, followed by quantitative RT-PCR and validation of selected markers in the serum of patients at the protein level. Results: In total, 896 significantly differentially expressed genes were identified (p ≤ 0.05). After restricting these to molecules present in the circulation, 9 upregulated and 5 downregulated genes were selected. Four of them (β-hCG, HTRA4, LHB1, all upregulated; and NOX4, downregulated) were validated by quantitative real-time RT-PCR. Finally, the maternal plasma protein levels of 2 of these genes (LHB and β-hCG) were confirmed to be significantly different between preeclampsia cases and controls. Discussion: We identified 14 potential new biomarker candidates for preeclampsia and validated 4 of them by quantitative RT-PCR and 2 of them with subsequent serum protein analyses. Further studies will assess the optimal marker combination for the imminent prediction of impending preeclampsia.

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Section: Discussionsupporting

confidence: 93%

Microarray Screening for Novel Preeclampsia Biomarker Candidates

Lapaire¹,

Grill²,

Lalevée³

et al. 2012

Fetal Diagn Ther

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“…Therefore they proposed that the N-terminal domain may function as a redox-sensing element that regulates autoproteolytic activity of HtrA1 in vivo depending on the cellular redox state [114]. Their conclusion is closely connected to the earlier findings showing that HtrA1 undergoes a limited proteolytic processing [24,115,116]. Chien et al [24] demonstrated that in response to paclitaxel treatment of ovarian cancer cells HtrA1 underwent autocatalytic cleavage resulting in generation of the protease variant lacking the N-terminal domain.…”

Section: Structural Features Of Htra1mentioning

confidence: 83%

Structural insights into the activation mechanisms of human HtrA serine proteases

Żurawa-Janicka

Wenta

Jarzab

et al. 2017

Archives of Biochemistry and Biophysics

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“…The transcription of this gene is highly regulated both during development and in the adult (35,36), and in particular, it has been shown that HtrA1 is upregulated during the progress of human pregnancy, suggesting an important role of this protein in placental formation and function (37,38). It is known that HtrA1 expression is decreased in progression and invasion of ovarian and endometrial cancers, melanomas, lung cancer, and mesotheliomas (10-13, 39, 40), and it is also involved in chemotherapyinduced apoptosis (32).…”

Section: Discussionmentioning

confidence: 99%

The Serine Protease HtrA1 Specifically Interacts and Degrades the Tuberous Sclerosis Complex 2 Protein

Campioni

Severino

Manente

et al. 2010

Molecular Cancer Research

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Hamartin and tuberin are products of the tumor suppressor genes TSC1 and TSC2, respectively. Mutations affecting either gene result in the tuberous sclerosis syndrome, a neurologic genetic disorder characterized by the formation of multiple benign tumors or hamartomas. In this study, we report the identification of TSC2, but not TSC1, as a substrate of HtrA1, a member of the human HtrA family proteins of serine proteases. We show the direct interaction and colocalization in the cytoplasm of HtrA1 and TSC2 and that HtrA1 cleaves TSC2 both in vitro and in vivo. Finally, we show that alterations in HtrA1 expression cause modifications in phosphorylation status of two downstream targets of TSC2: 4E-BP1 and S6K. Our data suggest that, under particular physiologic or pathologic conditions, HtrA1 degrades TSC2 and activates the downstream targets. Considering that HtrA1 levels are significantly increased during embryogenesis, we speculate that one of the targets of HtrA1 activity during fetal development is the TSC2-TSC1 pathway. Mol Cancer Res; 8(9); 1248-60. ©2010 AACR.

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Expression Patterns of Two Serine Protease HtrA1 Forms in Human Placentas Complicated by Preeclampsia with and without Intrauterine Growth Restriction

Cited by 46 publications

References 33 publications

Microarray Screening for Novel Preeclampsia Biomarker Candidates

Microarray Screening for Novel Preeclampsia Biomarker Candidates

Structural insights into the activation mechanisms of human HtrA serine proteases

The Serine Protease HtrA1 Specifically Interacts and Degrades the Tuberous Sclerosis Complex 2 Protein

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