Promotion of self-renewal of embryonic stem cells by midkine.
OBJECTIVE
To characterize the expression and function of midkine (MK) in an in vitro embryonic stem cell (ESC) culture system.


METHODS
To investigate the potential roles of MK, the expression of MK in ESCs was evaluated by RT-PCR and immunocytochemistry. The effects of MK on the self-renewal of ESCs were measured using alkaline phosphatase assays, immunocytochemistry, RT-PCR and colony-forming assays. The mechanism of the growth-promoting effect of MK in mESCs was assessed by cell cycle analysis and Western blot analysis.


RESULTS
MK is expressed in mouse embryonic stem cells (mESCs), human embryonic stem cells (hESCs) and mouse embryonic fibroblasts (MEFs). MK promotes proliferation and self-renewal of mESCs both in feeder and feeder free culture systems. It also promotes self-renewal and proliferation of hESCs. Further study showed that MK promotes the growth of mESCs by inhibiting apoptosis while accelerating the progression toward the S phase, and enhances mESC self-renewal through PI3K/Akt signaling pathway.


CONCLUSIONS
MK plays profound roles in ESCs. MK/PTPzeta signaling pathway is a novel pathway in the signal network maintaining pluripotency of ESCs. The results extend our knowledge on pluripotency control of ESCs and the relationship between ESCs and cancers.
Yao
Xing
X
Huzhou Central Hospital, Huzhou 313000, China. yaoy@mail.huptt.zj.cn
Tan
Zhou
Z
Gu
Bin
B
Wu
Rong-rong
RR
Liu
Yu-kan
YK
Dai
Li-cheng
LC
Zhang
Ming
M
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D000078792:Midkine; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
D016207:Cytokines; D000078792:Midkine; D019869:Phosphatidylinositol 3-Kinases; D017027:Protein Tyrosine Phosphatases