Emerging Role of SUMOylation in Placental Pathology

D. Baczyk a,*, S. Drewlo a,1, J.C.P. Kingdom a,b
Introduction

Preeclampsia is one of the most common placental disease states that can be experienced during pregnancy.  With common symptoms such as hypertension and proteinurea, preeclampsia can cause serious injuries to both the mother and the fetus, including death, if not treated.  One cause thought to induce preeclampsia is SUMOylation of placental development regulating factors such as GMC1. SUMO, refering to small ubiquitan related-modifier, in a non disease state is attached to target proteins via isopeptide bonds and is responsable for the regulation of nuclear proteins.  However, UBC9 mediated SUMOylation can be stimulated under certain external conditions such as hypoxia or ROS.  Ultimately, leading to decreased transcription activity.

Goal
Determine whether SUMOylation is upregulated in pateints with preeclampsia, and whether this upregualtion is due to UBC9?

Methods

Tissue Collection

Immunohistochemistry

Reverse Transcription and qRT-PCR

Western Blotting

Results 

• ·        Using qRT-PCR mRNA expression levels of SUMO1 were found to be elevated in IUGR and Preeclamsia patients compared to healthy women in the early first, late first, and 2^nd trimesters. Whereas, the SUMO2 and SUMO3 proteins were found to have higher expression levels only in preeclamsia patients.
• ·         This was then followed by Western Blotting which also showed increased protein levels of SUMO1/2/3 in patients with PE vs. the age matched controls.
• ·         They next wanted to evaluate the effects of UBC9 on SUMOylation, so qRT-PCR was performed for the second time along with western blotting examining the levels of mRNA and protein expression for UBC9.  The results revealed increased levels of both mRNA and protein expression in preeclamsia patients compared to the age-related control group.
• ·         The last tests done were qRT-PCR on placental tissues cultured under hypoxic conditions for 3hrs and 24hrs.  Interestingly, after three hours of hypoxia mRNA levels of UBC9 and SUMO1/2/3 were significantly increased compared to the control tissues cultured under normal conditions.  However, after 24 hours of hypoxic conditions this was not the case. None of the mRNA levels tested after 24 hours were found to have significantly increased.

Future Studies

As novel as this study was, there was no mechanism shown liking UBC9 mediation to SUMOylation which should be done in the future.