title: Improvement of radiotherapy-induced lacrimal gland injury by induced pluripotent stem cell-derived conditioned medium via MDK and inhibition of the p38/JNK pathway.
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.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. doczyq@163.com.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Plastic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200031, China. alcee@126.com.
authors.forename: Chenliang
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. rtpcr@163.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. dacier@126.com.
authors.forename: Mingui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China. googqq@126.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017077:Culture Media, Conditioned / Q000302:isolation & purification / Q000494:pharmacology*; D016207:Cytokines / Q000302:isolation & purification / Q000494:pharmacology; D005260:Female; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000078792:Midkine; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011837:Radiation-Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D009414:Nerve Growth Factors; D011837:Radiation-Protective Agents; D000078792:Midkine; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases