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Int. J. Mol. Sci. 2014, 15(10), 18407-18421; doi:10.3390/ijms151018407

Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway

1
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China
2
Department of Plastic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200031, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 1 August 2014 / Revised: 24 September 2014 / Accepted: 28 September 2014 / Published: 13 October 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: radiotherapy; P38; lacrimal gland; induced pluripotent stem cell radiotherapy; P38; lacrimal gland; induced pluripotent stem cell
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhang, Y.; Deng, C.; Qian, J.; Zhang, M.; Li, X. Improvement of Radiotherapy-Induced Lacrimal Gland Injury by Induced Pluripotent Stem Cell-Derived Conditioned Medium via MDK and Inhibition of the p38/JNK Pathway. Int. J. Mol. Sci. 2014, 15, 18407-18421.

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