Abstract:
OBJECTIVE:Receptor-activator of NF-κB ligand (TNFSF11, also known as RANKL) and its receptor RANK are essential regulators on bone remodeling, mammary gland development and hormone-associated breast cancer development. However, the expression pattern and role of RANKL/RANK axis in decidual stromal cells (DSCs) are unclear in human early pregnancy. STUDY DESIGN:We analyzed RANKL/RANK expression in DSCs by real-time PCR, immunhistochemistry, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Then BrdU cell proliferation assay, flow cytometry assay and ELISA were performed to investigate the effect of recombinant human RANKL and DSCs-derived RANKL on the proliferation, apoptosis, chemokine (C-C motif) ligand 2 (CCL2) secretion, C-C chemokine receptor type 2 (CCR2) and other target proteins expression in DSCs in vitro, respectively. RESULTS:Here we show that DSCs co-express RANKL/RANK. Not only recombinant human (rh) RANKL but also the DSC-secreted RANKL stimulate proliferation and anti-apoptosis, and elevate CCL2 secretion and CCR2 expression of DSCs. Furthermore, the stimulatory effects on the proliferation, anti-apoptosis and the expression of Bcl-2 and Ki67 and inhibitory signaling on Fas ligand (FasL) in DSCs induced by RANKL can be partly reversed by the way of blocking CCL2 and or CCR2. CONCLUSIONS:Our results have revealed that RANKL/RANK signal promotes Bcl-2 and Ki67 and decreases FasL expression, and further as a positive regulator for stimulating the proliferation and growth of DSCs through up-regulating CCL2/CCR2 signal, which finally contributes to the establishment and maintenance of physiological pregnancy.
journal_name
Placentajournal_title
Placentaauthors
Meng YH,Li H,Chen X,Liu LB,Shao J,Chang KK,Du MR,Jin LP,Li MQ,Li DJdoi
10.1016/j.placenta.2013.04.020subject
Has Abstractpub_date
2013-08-01 00:00:00pages
663-71issue
8eissn
0143-4004issn
1532-3102pii
S0143-4004(13)00217-8journal_volume
34pub_type
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