Increased cystatin C expression in the pre-eclamptic placenta.
Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.
Kristensen
Karl
K
Department of Obstetrics and Gynaecology, University Hospital, Lund, Sweden. karl.kristensen@med.lu.se
Larsson
I
I
Hansson
S R
SR
D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D014327:Trophoblasts / Q000737:chemistry; D015854:Up-Regulation
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D012333:RNA, Messenger