Derek D Norman, Yoojin Shin, Louisa Balázs, Erzsébet Szabó, Zoltán Benyó, Sue Chin Lee, Gábor J Tigyi
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引用次数: 0
Abstract
Immediate early response gene-3 (IER3/IEX-1) encodes a radiation-inducible stress-response adaptor protein that integrates pro-survival signaling pathways, yet the upstream mechanisms regulating its expression after irradiation remain incompletely understood. Here we investigated whether lysophosphatidic acid receptor (LPAR) signaling regulates IEX-1 expression during the radiation response and examined the radiobiological consequences of IEX-1 deficiency. LPAR activation enhanced IEX-1 expression in irradiated mouse whole blood, bone marrow, intestinal mucosa, and intestinal enteroids. In addition, IEX-1-deficient mice exhibited increased susceptibility to lethal radiation injury after total-body or partial body irradiation, while IEX-1-deficient enteroids displayed delayed growth and altered ERK phosphorylation kinetics. Together, these findings identify IEX-1 as a previously unrecognized downstream target of LPAR signaling after irradiation.
期刊介绍：
Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology
and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically
ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or
biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with
chemical agents contributing to the understanding of radiation effects.
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