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Synergistic effect of high glucose and ANG II on proliferation of mouse embryonic stem cells: Involvement of PKC and MAPKs as well as AT1 receptor
Author(s) -
Kim Yun Hee,
Han Ho Jae
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21314
Subject(s) - endocrinology , angiotensin ii , medicine , receptor , cell growth , embryonic stem cell , population , chemistry , angiotensin ii receptor type 1 , biology , microbiology and biotechnology , biochemistry , gene , environmental health
This study examined the synergistic effect of high glucose levels and ANG II on proliferation and its related signal pathways using mouse embryonic stem (ES) cells. The combined use of a high glucose concentration (25 mM) and ANG II increased the level of [ 3 H]thymidine/BrdU incorporation, and the number of cells compared with either treatment alone. Each treatment with high glucose or ANG II increased the cell population in the S phase compared with control, and the combined treatment of a high glucose concentration and ANG II significantly increased the number of cells in the S phase according to FACS analysis. Moreover, the high glucose‐induced increase in [ 3 H]thymidine incorporation was blocked by inhibiting the ANG II type 1 (AT1) receptor. The combined high glucose and ANG II significantly increased the STAT3 phosphorylation compared with high glucose or ANG II alone. ANG II stimulated the influx of Ca 2+ in 25 mM glucose compared with 5 mM glucose. High glucose levels increase the level of PKC α, ε, and ζ translocation from the cytosol to the membrane fraction. In an examination of other signal pathways, the combined treatment significantly increased the level of p44/42, p38 MAPKs phosphorylation compared with either treatment alone. Indeed, the combined treatment increased the mRNA expression level of the protooncogenes and cell cycle regulatory proteins. In conclusion, the combined treatment of a high glucose concentration and ANG II had a synergistic effect in stimulating mouse ES cell proliferation through the Ca 2+ /PKC, MAPKs, and the AT1 receptor. J. Cell. Physiol. 215: 374–382, 2008. © 2007 Wiley‐Liss, Inc.