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 TGFβRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.
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 TGFβRIII 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 TGFβRIII, rather than endoglin, would be more effective in alleviating the inhibition of both TGF-β1 and TGF-β2 signaling in PE.