Progestin induced heart and neural crest derivatives expressed transcript 2 is associated with fibulin 1 expression in human endometrial stromal cells

Progestin-induced heart and neural crest derivatives expressed transcript 2 contributes to fibulin-1 expression in human endometrial stromal cells.


Hisayuu Cho, M.D., Hidetaka Okada, M.D., Tomoko Tsuzuki, M.D., Akemi Nishigaki, Ph.D., Katsuhiko Yasuda, M.D., Hideharu Kanzaki, M.D.

Volume 99, Issue 1, Pages 248-255.e2, January 2013



To investigate whether heart and neural crest derivatives expressed transcript 2 (HAND2) regulates fibulin-1 (FBLN1) expression during decidualization of human endometrial stromal cells (ESCs).


In vitro experiment.


Research laboratory.


Twenty-four patients undergoing hysterectomy for benign reasons.


ESCs were cultured with various progestins (medroxyprogesterone acetate [MPA], norethisterone, levonorgestrel, dienogest, and P), E2, dexamethasone, and/or 8-bromoadenosine 3′, 5′-cyclic monophosphate (8-Br-cAMP). HAND2 and FBLN1 were silenced by small interfering RNA technology.

Main Outcome Measure(s):

HAND2 and FBLN1 expression levels were assessed by real-time polymerase chain reaction and Western blot analysis.


MPA or E2 + MPA increased HAND2 mRNA levels in ESCs in a time- and dose-dependent manner, and this stimulatory effect was blocked by RU-486 (P receptor antagonist). HAND2 was increased by E2 + MPA earlier than FBLN1. Simultaneous MPA and 8-Br-cAMP treatment synergistically enhanced HAND2 mRNA levels. P and all the progestins significantly increased HAND2 mRNA levels, whereas E2, 8-Br-cAMP, or dexamethasone alone had no effect. Silencing of HAND2 expression significantly reduced FBLN1 expression, whereas FBLN1 silencing had no effect on HAND2 expression.


These results suggest that progestin-induced HAND2 contributes to FBLN1 expression in human ESCs.

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