Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-β signaling

Yao Wang, Qi Chen, Min Zhao, Kelly Walton, Craig Harrison, Guiying Nie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Context: Preeclampsia (PE) can be classified into early-onset (<34 weeks of gestation) and late-onset (>34 weeks of gestation) subtypes. Soluble endoglin, an auxiliary receptor for transforming growth factor (TGF)-β ligands, is increased in PE circulation and believed to inhibit TGF-β action by sequestering the ligands. However, soluble endoglin, with a low affinity to TGF-β ligands, has been demonstrated to have little effect by itself on TGF-β action. Objectives: We examined whether multiple soluble TGF-β receptors are elevated in PE circulation and whether they synergistically block TGF-β signaling. Design: TGF-β receptors were measured using enzyme-linked immunosorbent assay in sera collected from preeclamptic pregnancies and gestation-age-matched controls. TGF-β signaling was assessed using an in vitro bioassay and a tube formation assay. Results: TGF-β type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset PE. Endoglin was increased in both subtypes. At the greatest concentrations detected in PE, none of these soluble TGF-β receptors alone, including endoglin, inhibited TGF-β signaling. However, when all four soluble receptors were present, signaling of both TGF-β1 and TGF-β2 was substantially reduced. Removal of any one of these soluble receptors alleviated TGF-β1 inhibition; however, removal of soluble TGFbRIII was necessary to relieve TGF-β2 inhibition. Conclusions: Multiple soluble TGF-β receptors are present in pregnant circulation and elevated in early-onset PE; they synergistically inhibit TGF-β signaling, which might be more likely to occur in early-onset than late-onset PE. Reducing soluble TGFbRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.

Original languageEnglish
Pages (from-to)3065-3074
Number of pages10
JournalJournal of Clinical Endocrinology and Metablism
Volume102
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017

Cite this

@article{8c51cbf140c640eca6bdf547298ea73e,
title = "Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-β signaling",
abstract = "Context: Preeclampsia (PE) can be classified into early-onset (<34 weeks of gestation) and late-onset (>34 weeks of gestation) subtypes. Soluble endoglin, an auxiliary receptor for transforming growth factor (TGF)-β ligands, is increased in PE circulation and believed to inhibit TGF-β action by sequestering the ligands. However, soluble endoglin, with a low affinity to TGF-β ligands, has been demonstrated to have little effect by itself on TGF-β action. Objectives: We examined whether multiple soluble TGF-β receptors are elevated in PE circulation and whether they synergistically block TGF-β signaling. Design: TGF-β receptors were measured using enzyme-linked immunosorbent assay in sera collected from preeclamptic pregnancies and gestation-age-matched controls. TGF-β signaling was assessed using an in vitro bioassay and a tube formation assay. Results: TGF-β type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset PE. Endoglin was increased in both subtypes. At the greatest concentrations detected in PE, none of these soluble TGF-β receptors alone, including endoglin, inhibited TGF-β signaling. However, when all four soluble receptors were present, signaling of both TGF-β1 and TGF-β2 was substantially reduced. Removal of any one of these soluble receptors alleviated TGF-β1 inhibition; however, removal of soluble TGFbRIII was necessary to relieve TGF-β2 inhibition. Conclusions: Multiple soluble TGF-β receptors are present in pregnant circulation and elevated in early-onset PE; they synergistically inhibit TGF-β signaling, which might be more likely to occur in early-onset than late-onset PE. Reducing soluble TGFbRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.",
author = "Yao Wang and Qi Chen and Min Zhao and Kelly Walton and Craig Harrison and Guiying Nie",
year = "2017",
month = "8",
day = "1",
doi = "10.1210/jc.2017-01150",
language = "English",
volume = "102",
pages = "3065--3074",
journal = "Journal of Clinical Endocrinology and Metablism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "8",

}

Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-β signaling. / Wang, Yao; Chen, Qi; Zhao, Min; Walton, Kelly; Harrison, Craig; Nie, Guiying.

In: Journal of Clinical Endocrinology and Metablism, Vol. 102, No. 8, 01.08.2017, p. 3065-3074.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Multiple soluble TGF-β receptors in addition to soluble endoglin are elevated in preeclamptic serum and they synergistically inhibit TGF-β signaling

AU - Wang, Yao

AU - Chen, Qi

AU - Zhao, Min

AU - Walton, Kelly

AU - Harrison, Craig

AU - Nie, Guiying

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Context: Preeclampsia (PE) can be classified into early-onset (<34 weeks of gestation) and late-onset (>34 weeks of gestation) subtypes. Soluble endoglin, an auxiliary receptor for transforming growth factor (TGF)-β ligands, is increased in PE circulation and believed to inhibit TGF-β action by sequestering the ligands. However, soluble endoglin, with a low affinity to TGF-β ligands, has been demonstrated to have little effect by itself on TGF-β action. Objectives: We examined whether multiple soluble TGF-β receptors are elevated in PE circulation and whether they synergistically block TGF-β signaling. Design: TGF-β receptors were measured using enzyme-linked immunosorbent assay in sera collected from preeclamptic pregnancies and gestation-age-matched controls. TGF-β signaling was assessed using an in vitro bioassay and a tube formation assay. Results: TGF-β type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset PE. Endoglin was increased in both subtypes. At the greatest concentrations detected in PE, none of these soluble TGF-β receptors alone, including endoglin, inhibited TGF-β signaling. However, when all four soluble receptors were present, signaling of both TGF-β1 and TGF-β2 was substantially reduced. Removal of any one of these soluble receptors alleviated TGF-β1 inhibition; however, removal of soluble TGFbRIII was necessary to relieve TGF-β2 inhibition. Conclusions: Multiple soluble TGF-β receptors are present in pregnant circulation and elevated in early-onset PE; they synergistically inhibit TGF-β signaling, which might be more likely to occur in early-onset than late-onset PE. Reducing soluble TGFbRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.

AB - Context: Preeclampsia (PE) can be classified into early-onset (<34 weeks of gestation) and late-onset (>34 weeks of gestation) subtypes. Soluble endoglin, an auxiliary receptor for transforming growth factor (TGF)-β ligands, is increased in PE circulation and believed to inhibit TGF-β action by sequestering the ligands. However, soluble endoglin, with a low affinity to TGF-β ligands, has been demonstrated to have little effect by itself on TGF-β action. Objectives: We examined whether multiple soluble TGF-β receptors are elevated in PE circulation and whether they synergistically block TGF-β signaling. Design: TGF-β receptors were measured using enzyme-linked immunosorbent assay in sera collected from preeclamptic pregnancies and gestation-age-matched controls. TGF-β signaling was assessed using an in vitro bioassay and a tube formation assay. Results: TGF-β type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset PE. Endoglin was increased in both subtypes. At the greatest concentrations detected in PE, none of these soluble TGF-β receptors alone, including endoglin, inhibited TGF-β signaling. However, when all four soluble receptors were present, signaling of both TGF-β1 and TGF-β2 was substantially reduced. Removal of any one of these soluble receptors alleviated TGF-β1 inhibition; however, removal of soluble TGFbRIII was necessary to relieve TGF-β2 inhibition. Conclusions: Multiple soluble TGF-β receptors are present in pregnant circulation and elevated in early-onset PE; they synergistically inhibit TGF-β signaling, which might be more likely to occur in early-onset than late-onset PE. Reducing soluble TGFbRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.

UR - http://www.scopus.com/inward/record.url?scp=85026918707&partnerID=8YFLogxK

U2 - 10.1210/jc.2017-01150

DO - 10.1210/jc.2017-01150

M3 - Article

VL - 102

SP - 3065

EP - 3074

JO - Journal of Clinical Endocrinology and Metablism

JF - Journal of Clinical Endocrinology and Metablism

SN - 0021-972X

IS - 8

ER -