Decreased intracellular pH induced by cariporide differentially contributes to human umbilical cord-derived mesenchymal stem cells differentiation.
OBJECTIVE
Na+/H+ exchanger 1 (NHE1) is an important regulator of intracellular pH (pHi). High pHi is required for cell proliferation and differentiation. Our previous study has proven that the pHi of mesenchymal stem cells is higher than that of normal differentiated cells and similar to tumor cells. NHE1 is highly expressed in both mesenchymal stem cells and tumor cells. Targeted inhibition of NHE1 could induce differentiation of K562 leukemia cells. In the present paper we explored whether inhibition of NHE1 could induce differentiation of mesenchymal stem cells.


METHODS
MSCs were obtained from human umbilical cord and both the surface phenotype and functional characteristics were analyzed. Selective NHE1 inhibitor cariporide was used to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The pHi and the differentiation of hUC-MSCs were compared upon cariporide treatment. The putative signaling pathway involved was also explored.


RESULTS
The pHi of hUC-MSCs was decreased upon cariporide treatment. Cariporide up-regulated the osteogenic differentiation of hUC-MSCs while the adipogenic differentiation was not affected. For osteogenic differentiation, β-catenin expression was up-regulated upon cariporide treatment.


CONCLUSIONS
Decreased pHi induced by cariporide differentially contributes to hUC-MSCs differentiation.
State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Wei
W
Gao
Hairui
H
Zhang
Guoqiang
G
Chang
Zhenqing
Z
Xie
Hanyu
H
Wang
Li
L
Ma
Zhongchao
Z
Han
Qinghua
Q
Li
Tianxiang
T
Pang
D050156:Adipogenesis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
D027682:Cation Transport Proteins; D006146:Guanidines; D034741:RNA, Small Interfering; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D051176:beta Catenin; C093373:cariporide