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Retinoic acid promotes proliferation of chicken primordial germ cells via activation of PI3K/Akt‐mediated NF‐κB signalling cascade
Author(s) -
Yu Minli,
Ge Chutian,
Zeng Weidong,
Mi Yuling,
Zhang Caiqiao
Publication year - 2012
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20110542
Subject(s) - pi3k/akt/mtor pathway , biology , protein kinase b , microbiology and biotechnology , retinoic acid , ly294002 , kinase , signal transduction , cancer research , biochemistry , gene
As embryonic progenitors for the gametes, PGCs (primordial germ cells) proliferate and develop under strict regulation of numerous intrinsic and external factors. As the most active natural metabolite of vitamin A, all‐trans RA (retinoic acid) plays pivotal roles in regulating development of various cells. The proliferating action of RA on PGCs was investigated along with the intracellular PI3K (phosphoinositide 3‐kinase)/Akt (protein kinase B; also known as Akt)‐mediated NF‐κB (nuclear factor κB) signalling cascade. The results show that RA significantly promoted PGC proliferation in a dose‐ and time‐dependent manner, confirmed by BrdU (bromodeoxyuridine) incorporation and cell cycle analysis. However, this promoting effect was attenuated by sequential inhibitors of LY294002 for PI3K, KP372‐1 for Akt and SN50 for NF‐κB respectively. Western blot analysis showed increased Akt phosphorylation (Ser 473 ) of PGCs after stimulation with RA, but this was abolished by LY294002 or KP372‐1. Treatment with RA increased expression of NF‐κB and decreased IκBα (inhibitory κBα) expression, which were inhibited by SN50. Blockade of PI3K or Akt activity inhibited NF‐κB translocation from the cytoplasm to the nucleus. Finally, mRNA expression of cell cycle regulating genes [cyclin D1 and E, CDK6 (cyclin‐dependent kinase 6) and CDK2 ] was up‐regulated in the RA‐treated cells. This stimulation was also markedly retarded by combined treatment with LY294002, KP372‐1 and SN50. These results suggest that RA activates the PI3K/Akt and NF‐κB signalling cascade to promote proliferation of the cultured chicken PGCs.