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Actin polymerization-enhancing drugs promote ovarian follicle growth mediated by
the Hippo signaling effector YAP
#MMPMID25690654
Cheng Y
; Feng Y
; Jansson L
; Sato Y
; Deguchi M
; Kawamura K
; Hsueh AJ
FASEB J
2015[Jun]; 29
(6
): 2423-30
PMID25690654
show ga
Hippo signaling pathway consists of conserved serine/threonine kinases to
maintain optimal organ sizes. Studies have demonstrated that fragmentation of
murine ovaries increases actin polymerization and disrupts Hippo signaling,
leading to nuclear translocation of Hippo signaling effector Yes-associated
protein (YAP) in ovarian follicles and follicle growth. For patients with
polycystic ovarian syndrome showing follicle arrest, ovarian wedge resection and
laser drilling promote follicle growth. Because these damaging procedures likely
involve actin polymerization, we tested whether actin polymerization-promoting
drugs could promote YAP translocation and stimulate follicle growth. Treatment of
murine ovaries with ?M Jasplakinolide (JASP), an actin polymerization-promoting
cyclic peptide, or sphingosine-1-phosphate (S1P), a follicular fluid constituent
known to promote actin polymerization, increased the conversion of globular actin
to the filamentous form, followed by increased nuclear YAP and expression of
downstream connective tissue growth factor (CCN2). After short-term treatments
with JASP or S1P, in vitro cultured and in vivo grafted ovaries showed follicle
growth. Furthermore, induction of constitutively active YAP in ovarian grafts of
transgenic mice enhanced follicle development, whereas treatment of human ovarian
cortices with JASP or S1P increased CCN2 expression. Thus, JASP and S1P stimulate
follicle growth and are potential therapeutic agents for treating polycystic
ovarian syndrome and other ovarian disorders.
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