Abstract
This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O 2) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3′ UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3′ UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.
| Original language | English |
|---|---|
| Pages (from-to) | 590-602 |
| Number of pages | 13 |
| Journal | American Journal of Pathology |
| Volume | 179 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2011 Aug 1 |
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All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
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MiR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines : Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies. / Lee, Deug Chan; Romero, Roberto; Kim, Jung Sun; Tarca, Adi L.; Montenegro, Daniel; Pineles, Beth L.; Kim, Ernest; Lee, Joonho; Kim, Sun Young; Draghici, Sorin; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai.
In: American Journal of Pathology, Vol. 179, No. 2, 01.08.2011, p. 590-602.Research output: Contribution to journal › Article
TY - JOUR
T1 - MiR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines
T2 - Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies
AU - Lee, Deug Chan
AU - Romero, Roberto
AU - Kim, Jung Sun
AU - Tarca, Adi L.
AU - Montenegro, Daniel
AU - Pineles, Beth L.
AU - Kim, Ernest
AU - Lee, Joonho
AU - Kim, Sun Young
AU - Draghici, Sorin
AU - Mittal, Pooja
AU - Kusanovic, Juan Pedro
AU - Chaiworapongsa, Tinnakorn
AU - Hassan, Sonia S.
AU - Kim, Chong Jai
PY - 2011/8/1
Y1 - 2011/8/1
N2 - This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O 2) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3′ UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3′ UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.
AB - This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O 2) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3′ UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3′ UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.
UR - http://www.scopus.com/inward/record.url?scp=80052498029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052498029&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2011.04.035
DO - 10.1016/j.ajpath.2011.04.035
M3 - Article
C2 - 21801864
AN - SCOPUS:80052498029
VL - 179
SP - 590
EP - 602
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -