title: Expression patterns of two serine protease HtrA1 forms in human placentas complicated by preeclampsia with and without intrauterine growth restriction.
abstract: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are pregnancy-specific disorders that have in common abnormal placental implantation, a marked proliferation of villous cytotrophoblastic cells and focal necrosis of the syncytiotrophoblast. Several studies show an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the feto-placental unit. The cause of PE is a matter of debate, but recently studies in mice suggest that the primary feto-placental lesions are sufficient to initiate the disease. HtrA1, a member of the family of HtrA proteins, is a secreted multidomain protein with serine protease activity. It is expressed in first and third trimester of gestation. In specimens from the first trimester of gestation, immunostaining for HtrA1 is generally found in both layers of villous trophoblast, syncytiotrophoblast and cytotrophoblast. Cytoplasm of extravillous trophoblast and extracellular matrix of cell islands and cell columns are labeled for HtrA1. Specimens from third trimester of gestation show a more intense positivity for HtrA1 in the syncytiotrophoblast than in cytotrophoblast. The extravillous trophoblast and the decidual cells, is positive for HtrA1. The purpose of this study is to investigate the expression pattern of HtrA1 in placentas from PE without IUGR (maternal PE) and with IUGR (fetal PE) by quantitative western blotting and immunohistochemistry. By quantitative western blotting analysis we observed a significant upregulation of approximately 30 kDa HtrA1 form in PE. Differently, we detected a significant total HtrA1 down-regulation in PE-IUGR. Moreover, immunostaining for HtrA1 was positive in the villous trophoblast, in the syncytial knots and irregularly in the fetal vessel walls in PE placentas while immunostaining for HtrA1was present particularly in the syncytial knots in PE-IUGR placentas. In conclusion, we suggest that the approximately 30 kDa HtrA1 form can be correlated to maternal PE while that the significant down-regulation of total HtrA1 can be correlated to placental PE. These HtrA1 alterations could be considered as possible markers to discriminate placental PE from maternal PE.
authors.affiliation: Institute of Normal Human Morphology, Faculty of Medicine, Polytechnic University of Marche, and Salesi Hospital, Via Tronto, 10/a, I-60020 Ancona, Italy. t.lorenzi@univpm.it
authors.forename: T
authors.initials: T
authors.lastname: Lorenzi
authors.forename: D
authors.initials: D
authors.lastname: Marzioni
authors.forename: S
authors.initials: S
authors.lastname: Giannubilo
authors.forename: A
authors.initials: A
authors.lastname: Quaranta
authors.forename: C
authors.initials: C
authors.lastname: Crescimanno
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: A
authors.initials: A
authors.lastname: Baldi
authors.forename: T
authors.initials: T
authors.lastname: Todros
authors.forename: A L
authors.initials: AL
authors.lastname: Tranquilli
authors.forename: M
authors.initials: M
authors.lastname: Castellucci
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007124:Immunoenzyme Techniques; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D020033:Protein Isoforms; D012697:Serine Endopeptidases / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases