WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell proliferation

Journal of Endocrinology - Tập 229 Số 2 - Trang 197-207 - 2016
Virginia Rider1, Alex Talbott1, Anuradha Bhusri1, Zach Krumsick1, Sierra Foster1, Joshua Wormington1, Bruce F. Kimler2
1Department of Biology, Pittsburg State University, Pittsburg, Kansas, USA
2Department of Radiation Oncology, The University of Kansas Medical Center, Kansas City, Kansas, USA

Tóm tắt

Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3β (GSK-3β) and stimulating β-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidateWntgenes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg/daily) rats, and progesterone-pretreated rats given a single dose (0.2µg) of estradiol. The spatial distribution of the WNT proteins was determined in the uteri after the same treatments.Wnt5aincreased in response to progesterone and the protein emerged in the periluminal stromal cells of progesterone-pretreated rat uteri. To investigate whether WNT5A was required for proliferation, uterine stromal cell lines were stimulated with progesterone (1µM) and fibroblast growth factor (FGF, 50ng/mL). Proliferating stromal cells expressed a two-fold increase in WNT5A protein at 12h post stimulation. Stimulated stromal cells were cultured with actinomycin D (25µg/mL) to inhibit new RNA synthesis. RelativeWnt5aexpression increased at 4 and 6 h of culture, suggesting that progesterone plus FGF preferentially increasedWnt5amRNA stability. Knockdown ofWnt5ain uterine stromal cell lines inhibited stromal cell proliferation and decreasedWnt5amRNA. The results indicate that progesterone initiates and synchronizes uterine stromal cell proliferation by increasing WNT5A expression and signaling.

Từ khóa


Tài liệu tham khảo

Bell, 1983, Decidualization: regional differentiation and associated function, Oxford Reviews in Reproductive Biology, 5, 220

10.1007/978-0-387-78818-0_12

10.1016/j.celrep.2014.06.027

10.1038/nsmb912

10.1210/er.2003-0020

10.1095/biolreprod.111.091769

10.1016/bs.ircmb.2014.10.003

10.1677/joe.0.0390593

10.1096/fj.10-175349

10.1096/fj.11-193334

10.1387/ijdb.140011da

10.1095/biolreprod.108.075416

10.1095/biolreprod.110.088161

10.1038/onc.2008.363

10.1210/en.141.2.637

Katoh, 2007, STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (Review), International Journal of Molecular Medicine, 19, 273

10.1242/dev.019810

10.1210/en.2012-1585

10.1101/gad.9.18.2266

10.1677/joe.0.0410363

10.1242/dev.01090

Miller, 1998, Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract, Development, 125, 3201, 10.1242/dev.125.16.3201

10.1002/dvdy.21991

10.1095/biolreprod.103.025692

10.1073/pnas.0500612102

Nallasamy, 2012, Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium, PLoS Genetics, 8, 1, 10.1371/journal.pgen.1002500

10.1038/27221

Paul, 2008, Wnt signaling and cancer development: therapeutic implication, Neoplasma, 55, 165

10.1210/me.2014-1074

10.1210/jc.2007-2023

10.1095/biolreprod55.6.1333

10.1055/s-0029-1242989

Rider, 1994, Inhibition of progesterone receptor function results in loss of basic fibroblast growth factor expression and stromal cell proliferation during uterine remodeling in the pregnant rat, Journal of Endocrinology, 36, 239, 10.1677/joe.0.1400239

Rider, 1998, Progesterone-growth factor interactions in uterine stromal cells, Biology of Reproduction, 66, 188

10.1210/en.2003-0890

Rider, 2003, Increased estrogen-dependent expression of calcineurin in female SLE T cells is regulated by multiple mechanisms., Journal of Gender Specific Medicine, 6, 14

10.1677/joe.1.07030

10.1016/j.placenta.2010.07.011

10.1007/s10815-014-0409-7

10.1210/er.2014-1046

10.1038/17820

10.1095/biolreprod.112.105957

10.1101/gad.1424006

10.1210/me.2002-0290

10.1101/cshperspect.a011536

Thông tin
Thông tin xuất bản

Journal of Endocrinology

Tập 229 Số 2

197-207

Thông tin tác giả