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Perturbation of pla...
Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism
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- Yung, Hong Wa (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
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- Zhao, Xiaohui (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
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- Glover, Luke (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
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- Burrin, Charlotte (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
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- Pang, Poh-Choo (författare)
- Imperial Coll London, Dept Life Sci, London, England.
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- Jones, Carolyn J. P. (författare)
- Univ Manchester, Maternal & Fetal Hlth Ctr, Manchester Acad Hlth Sci Ctr, Manchester, England.
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- Gill, Carolyn (författare)
- Kings Coll London, Dept Women & Childrens Hlth, London, England.
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- Duhig, Kate (författare)
- Univ Manchester, Maternal & Fetal Hlth Ctr, Manchester Acad Hlth Sci Ctr, Manchester, England.;Kings Coll London, Dept Women & Childrens Hlth, London, England.
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- Olovsson, Matts, 1958- (författare)
- Uppsala universitet,Institutionen för kvinnors och barns hälsa
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- Chappell, Lucy C. (författare)
- Kings Coll London, Dept Women & Childrens Hlth, London, England.
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- Haslam, Stuart M. (författare)
- Imperial Coll London, Dept Life Sci, London, England.
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- Dell, Anne (författare)
- Imperial Coll London, Dept Life Sci, London, England.
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- Burton, Graham J. (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
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- Charnock-Jones, D. Stephen (författare)
- Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.;Univ Cambridge, Dept Obstet & Gynaecol, Cambridge CB2 0SW, England.
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Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England Imperial Coll London, Dept Life Sci, London, England. (creator_code:org_t)
- Cell Press, 2023
- 2023
- Engelska.
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 26:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with "protein glycosylation"and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
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Yung, Hong Wa
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Zhao, Xiaohui
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Glover, Luke
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Burrin, Charlott ...
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Pang, Poh-Choo
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Jones, Carolyn J ...
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Gill, Carolyn
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Duhig, Kate
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Olovsson, Matts, ...
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Chappell, Lucy C ...
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Haslam, Stuart M ...
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Dell, Anne
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Burton, Graham J ...
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Charnock-Jones, ...
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- MEDICIN OCH HÄLSOVETENSKAP
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Uppsala universitet