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Yanqing Zhang, Jiang Qian, Mingui Zhang; Improvement of Radiotherapy-induced lacrimal gland injury by IPS cell-derived conditioned medium via inhibition of P38/JNK pathway and cylindromatosis -dependent regulation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4614.
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© ARVO (1962-2015); The Authors (2016-present)
Radiation therapy is one of the most widely used and effective treatment for orbital tumor, but it causes the side effect of dry eye due to lacrimal gland damage. Exploring the mechanisms underlying the secondary injury caused by radiation might be helpful for developing effective radioprotective therapy. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSCM) on gamma-irradiation-induced lacrimal gland failure on experimental mice.
Female C57BL/6 mice were irradiated with a total dose of 15 Gy under general anaesthesia. Scintigraphy was performed before irradiation, three days and seven days after irradiation, with a subsequent excision of left side inferior lacrimal gland for histological examination. In the experimental group, conditioned medium from iPSCs (iPSC-CM) were injected through tail vein of the irradiated mice. Primary mouse LGE cell isolation and culture were performed, Gadd45a cDNA was transfected, and cell proliferation was determined. Gadd45a (Millipore), Akt, p-Akt, P38, p-P38, JNK, p-JNK, Erk 1/2 and p-Erk 1/2 were tested by western blot assay.
iPSCM markedly decrease radiotherapy induced inflammatory processes predominantly through suppressing P38/JNK signaling. Further signalling pathway analyses indicated that iPSC-CM can suppress Akt (Protein Kinase B, PKB) phosphorylation.
Our study indicates that inhibiting P38/JNK pathway or increasing CYLD might be a therapeutic target in radiation-induced lacrimal gland injury.
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