Abstract
Radiation therapy is the most widely used and effective treatment for orbital tumors, but it causes dry eye due to lacrimal gland damage. Induced pluripotent stem cell-derived conditioned medium (iPSC-CM) has been shown to rescue different types of tissue damage. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSC-CM) on gamma-irradiation-induced lacrimal gland injury (RILI) in experimental mice. In this study, we found that iPSC-CM ameliorated RILI. iPSC-CM markedly decreased radiotherapy induced inflammatory processes, predominantly through suppressing p38/JNK signaling. Further signaling pathway analyses indicated that iPSC-CM could suppress Akt (Protein Kinase B, PKB) phosphorylation. High levels of midkine (MDK) were also found in iPSC-CM and could be involved in lacrimal gland regeneration by promoting cell migration and proliferation. Thus, our study indicates that inhibiting the p38/JNK pathway or increasing the MDK level might be a therapeutic target for radiation-induced lacrimal gland injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Culture Media, Conditioned / isolation & purification
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Culture Media, Conditioned / pharmacology*
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Cytokines / isolation & purification
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Cytokines / pharmacology
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Female
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Induced Pluripotent Stem Cells / metabolism*
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lacrimal Apparatus / drug effects*
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Lacrimal Apparatus / metabolism
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Lacrimal Apparatus / pathology
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Lacrimal Apparatus / radiation effects*
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MAP Kinase Signaling System / drug effects
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Mice
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Mice, Inbred C57BL
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Midkine
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Nerve Growth Factors / isolation & purification
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Nerve Growth Factors / pharmacology
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Radiation Injuries, Experimental / drug therapy*
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Radiation Injuries, Experimental / metabolism
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Radiation Injuries, Experimental / pathology
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Radiation-Protective Agents / isolation & purification
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Radiation-Protective Agents / pharmacology*
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Radiotherapy / adverse effects
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Radiotherapy / methods
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Culture Media, Conditioned
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Cytokines
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Nerve Growth Factors
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Radiation-Protective Agents
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Midkine
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases