Increase in Transforming Growth Factor-β Didnot Affect Trombospondin1 in Preeclampsia Placentas

Objective: The abnormalities of the placental growth process are a theory causing pre-eclampsia. Antiangiogenic factors contributed to it, such as thrombospondin-1 (TSp-1) that could stimulate transforming growth factor-beta (TGF-β), or vice versa. Some research showed that an increase in TGF-β did not always figurized its signaling. Therefore, we conducted a study to examine the TGF-β signaling proteins through its receptors and TSp-1 expression in preeclampsia placentas.

Materials And Methods: This observational study used 33 normal and 33 pre-eclampsia placental storaged samples, for examination of TGF-β and TGF-βR 1 and 2, SMAD2 using ELISA, and SMAD2 and TSp-1 mRNA using the reverse transcription polymerase chain reaction method. Data were analyzed using SPSS version 20.0, normality test by Kolmogorov-Smirnov, and significancy was analyzed using nonparametric Mann-Whitney test, or t-test for parametric, with confidence interval 95%. Spearman correlation was used for non-parametric data, besides the Pearson correlation for parametric data.

Results: Results showed that there were significant differences between preeclampsia and normal placenta in TGF-β, its receptors, SMAD2, and TSp-1 mRNA. Normal-TGF-β=1.19 (0.713-2.051) pg/mg; preeclampsia-TGFB=2.69 (0.906-10.252) pg/mg; p=0.001; normal-TGFBR1=1.025 (0.622-1.402) ng/mg; preeclampsia-TGFBR1=1.223 (0.372-2.553) ng/mg; p=0.004; Normal-TGF-βR2=0.959 (0.644-1.634) pg/mg; preeclampsia-TGFBR2=1.490 (0.775-3.645) pg/mg; p=0.0001; normal-SMAD2=2.087 (1.279-4.300) ng/mg; preeclampsia-SMAD2=3.508 (1.842-22.489) ng/mg; p=0.0001. The SMAD2 mRNA relative expression (Livax) in the normal placenta was=0.71 (0.03-7.25); pre-eclampsia placenta (PE)=0.49 (0.01-40.71); p=0.075, the normal TSp-1 mRNA expression=1.08 (0.09-5.31); PE=0.21 (0.002-24.06); p=0.002. The correlation test showed a strong correlation between TGF-β with TGFBR1 and 2 in the normal placenta, conversely, there was no correlation in the preeclampsia placenta. There was also no correlation between SMAD2 and TSp-1 mRNA in both normal and pre-eclampsia.

Conclusion: TGF-β signaling in the preeclampsia placenta was changed due to the increased of the protein signaling it self without correlation between TGF-β to its receptors and TSp-1 relative expression.