PMID- 24481225 OWN - NLM STAT- MEDLINE DCOM- 20160718 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 33 IP - 1 DP - 2014 TI - Decreased intracellular pH induced by cariporide differentially contributes to human umbilical cord-derived mesenchymal stem cells differentiation. PG - 185-94 LID - 10.1159/000356661 [doi] AB - BACKGROUND/AIMS: 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, beta-catenin expression was up-regulated upon cariporide treatment. CONCLUSION: Decreased pHi induced by cariporide differentially contributes to hUC-MSCs differentiation. FAU - Gao, Wei AU - Gao W AD - 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. FAU - Zhang, Hairui AU - Zhang H FAU - Chang, Guoqiang AU - Chang G FAU - Xie, Zhenqing AU - Xie Z FAU - Wang, Hanyu AU - Wang H FAU - Ma, Li AU - Ma L FAU - Han, Zhongchao AU - Han Z FAU - Li, Qinghua AU - Li Q FAU - Pang, Tianxiang AU - Pang T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140124 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Cation Transport Proteins) RN - 0 (Guanidines) RN - 0 (RNA, Small Interfering) RN - 0 (SLC9A1 protein, human) RN - 0 (Sodium-Hydrogen Exchanger 1) RN - 0 (Sodium-Hydrogen Exchangers) RN - 0 (Sulfones) RN - 0 (beta Catenin) RN - 7E3392891K (cariporide) SB - IM MH - Adipogenesis/drug effects MH - Cation Transport Proteins/metabolism MH - Cell Death/drug effects MH - Cell Differentiation/*drug effects MH - Gene Knockdown Techniques MH - Guanidines/*pharmacology MH - Humans MH - Hydrogen-Ion Concentration MH - Intracellular Space/drug effects/*metabolism MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Osteogenesis/drug effects MH - Phenotype MH - RNA, Small Interfering/metabolism MH - Sodium-Hydrogen Exchanger 1 MH - Sodium-Hydrogen Exchangers/metabolism MH - Sulfones/*pharmacology MH - Umbilical Cord/*cytology MH - Up-Regulation/drug effects MH - beta Catenin/metabolism EDAT- 2014/02/01 06:00 MHDA- 2016/07/19 06:00 CRDT- 2014/02/01 06:00 PHST- 2013/12/18 00:00 [accepted] PHST- 2014/02/01 06:00 [entrez] PHST- 2014/02/01 06:00 [pubmed] PHST- 2016/07/19 06:00 [medline] AID - 000356661 [pii] AID - 10.1159/000356661 [doi] PST - ppublish SO - Cell Physiol Biochem. 2014;33(1):185-94. doi: 10.1159/000356661. Epub 2014 Jan 24.