15-Deoxy-{delta}{sup 12,14}-Prostaglandin J{sub 2} regulates leukemia inhibitory factor signaling through JAK-STAT pathway in mouse embryonic stem cells
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States)
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States) and Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States) and Methodist Research Institute of Clarian Health, Indianapolis, IN 46202 (United States)
Embryonic stem (ES) cells are genetically normal, pluripotent cells, capable of self-renewal and differentiation into all cell lineages. While leukemia inhibitory factor (LIF) maintains pluripotency in mouse ES cells, retinoic acid and other nuclear hormones induce neuro-glial differentiation in mouse and human ES cells in culture. Peroxisome-proliferator-activated receptors (PPARs) are ligand-dependent nuclear receptor transcription factors that regulate cell growth and differentiation in many cell types. However, the role of PPARs in the regulation of ES cell growth and differentiation is not known. In this study, we show that LIF induces proliferation and self-renewal of mouse D3-ES cells in culture. However, treatment with 15-Deoxy-{delta}{sup 12,14}-Prostaglandin J{sub 2} (15d-PGJ2), a natural ligand for PPAR{gamma}, or all-trans retinoic acid (ATRA) results in a dose-dependent decrease in proliferation and self-renewal in D3-ES cells. Immunoprecipitation and Western blot analyses showed that LIF induces tyrosine phosphorylation of JAK1, TYK2 and STAT3 in 30 min and treatment with 15d-PGJ2 or ATRA results in a dose-dependent decrease in LIF-induced phosphorylation of JAK1 and STAT3 in D3-ES cells. However, treatment of D3-ES cells with Ciglitazone or 15d-PGJ2 for 48 h in culture resulted in a dose-dependent increase in PPAR{gamma} protein expression. These results suggest that PPAR{gamma} agonists regulate LIF signaling through JAK-STAT pathway leading to growth and self-renewal of ES cells.
- OSTI ID:
- 20858009
- Journal Information:
- Experimental Cell Research, Vol. 312, Issue 13; Other Information: DOI: 10.1016/j.yexcr.2006.04.010; PII: S0014-4827(06)00162-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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