dc.identifier.citation | O'Brien, M., Flynn, D., Mullins, B., Morrison, J.J., Smith, T.J. 'Expression of RHOGTPase regulators in human myometrium' (2008) 'Reproductive Biology and Endocrinology', 6, art. no. 1, . | en |
dc.description.abstract | Background: RHOGTPases play a significant role in modulating myometrial contractility in
uterine smooth muscle. They are regulated by at least three families of proteins, RHO guanine
nucleotide exchange factors (RHOGEFs), RHOGTPase-activating proteins (RHOGAPs) and RHO
guanine nucleotide inhibitors (RHOGDIs). RHOGEFs activate RHOGTPases from the inactive
GDP-bound to the active GTP-bound form. RHOGAPs deactivate RHOGTPases by accelerating
the intrinsic GTPase activity of the RHOGTPases, converting them from the active to the inactive
form. RHOGDIs bind to GDP-bound RHOGTPases and sequester them in the cytosol, thereby
inhibiting their activity. Ezrin-Radixin-Moesin (ERM) proteins regulate the cortical actin
cytoskeleton, and an ERM protein, moesin (MSN), is activated by and can also activate
RHOGTPases.
Methods: We therefore investigated the expression of various RHOGEFs, RHOGAPs, a
RHOGDI and MSN in human myometrium, by semi-quantitative reverse transcription PCR, real-
time fluorescence RT-PCR, western blotting and immunofluorescence microscopy. Expression of
these molecules was also examined in myometrial smooth muscle cells.
Results: ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN
mRNA and protein expression was confirmed in human myometrium at term pregnancy, at labour
and in the non-pregnant state. Furthermore, their expression was detected in myometrial smooth
muscle cells. It was determined that ARHGAP24 mRNA expression significantly increased at labour
in comparison to the non-labour state.
Conclusion: This study demonstrated for the first time the expression of the RHOGTPase
regulators ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN in
human myometrium, at term pregnancy, at labour, in the non-pregnant state and also in myometrial
smooth muscle cells. ARHGAP24 mRNA expression significantly increased at labour in comparison
to the non-labouring state. Further investigation of these molecules may enable us to further our
knowledge of RHOGTPase regulation in human myometrium during pregnancy and labour. | en |