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

Zhang, Yanqing; Deng, Chaohua; Jiao, Qian; Zhang, Mingui; Li, Xiaofeng

doi:10.3390/ijms151018407

Cited by 19 publications

(16 citation statements)

References 39 publications

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“…27 The activation of neutrophils is a complex process involving sequential phases with different signaling mediators, 28 and such phases can recruit neutrophils at damaged tissues in various conditions such as autoimmune diseases like Sjogren's syndrome or even radioactive treatments. 29 As well with the neutrophil levels, the levels of IL-1β, IL-6α and TNF-α increased significantly in DED mouse model, and decreased after LLLT. IL-1β, IL-6α, and TNF-α are well studied inflammatory cytokines, 30 Original Article leviate inflammation with controlling these cytokines.…”

Section: Discussionmentioning

confidence: 87%

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

et al. 2019

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Background and ObjectivesLow-level light therapy (LLLT) is an application of low-power light for various purposes such as promoting tissue repair, reducing inflammation, causing analgesia, etc. A previous study suggested the effect of light emitting diode (LED) light with the wavelength of 740 nm for promoting wound healing of corneal epithelial cells. This current study aimed to confirm the effect of LLLT for managing inflammation of a dry eye disease (DED) mouse model. Materials and MethodsA total of 50C57BL/6 female mice were randomly grouped into 5 groups to compare the effect of LLLT:1) Control group, 2) Only LLLT group, 3) Dry eye group, 4) LLLT in dry eye group, and 5) Early treatment group. DED was induced with 4 daily injections of scopolamine hydrobromide and desiccation stress for 17 days, and LLLT at 740 nm was conducted once every 3 days. To analyze the effect of LLLT on the DED mouse model, tear volume, corneal surface irregularities, and fluorescence in stained cores were measured, and the level of inflammation was assessed with immunohistochemistry. ResultsThe DED mouse model showed significant deterioration in the overall eye condition. After LLLT, the amount of tear volume was increased, and corneal surface irregularities were restored. Also, the number of neutrophils and the level of inflammatory cytokines significantly decreased as well. ConclusionThis study showed that LLLT at 740 nm was effective in controlling the corneal conditions and the degree of inflammation in DED. Such findings may suggest therapeutic effects of LLLT at 740 nm on DED.

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Section: Discussionmentioning

confidence: 87%

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

et al. 2019

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“…Zhang et al concluded that paracrine factors of iPSCs could inhibit stress‐induced senescence of H9C2 cardiomyocytes by inhibiting the p53‐p21 and p16‐pRb pathways . The stimulation of cell proliferation and anti‐apoptosis caused by iPS‐CM is mainly because of the secreted cytokines that do not cause tumour formation . There is the report that showed iPSCs and iPS‐CM have similar therapeutic effects on lung injury through the same signalling pathway .…”

Section: Introductionmentioning

confidence: 99%

Induced pluripotent stem cell‐conditional medium inhibits H9C2 cardiomyocytes apoptosis via autophagy flux and Wnt/β‐catenin pathway

Guo

Sohun

et al. 2019

J Cellular Molecular Medi

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Induced pluripotent stem cell‐derived conditioned medium ( iPS ‐ CM ) could improve cell viability in many types of cells and may be a better alternative for the treatment of myocardial infarction. This study aimed to examine the influence of iPS ‐ CM on anti‐apoptosis and the proliferation of H9C2 cardiomyocytes and investigate the underlying mechanisms. H9C2 cardiomyocytes were exposed to 200 μmol/L hydrogen peroxide (H 2 O 2 ) for 24 hours with or without pre‐treatment with iPS ‐ CM . The ratio of apoptotic cells, the loss of mitochondrial membrane potential (△Ψm) and the levels of intracellular reactive oxygen species were analysed by flow cytometric analysis. The expression levels of BCL ‐2 and BAX proteins were analysed by Western blot. Cell proliferation was assessed using cell cycle and EdU staining assays. To study cell senescence, senescence‐associated β‐galactosidase ( SA ‐β‐gal) staining was conducted. The levels of malondialdehyde, superoxide dismutase and glutathione were also quantified using commercially available enzymatic kits. The results showed that iPS ‐ CM containing basic fibroblast growth factor significantly reduced H 2 O 2 ‐induced H9C2 cardiomyocyte apoptosis by activating the autophagy flux pathway, promoted cardiomyocyte proliferation by up‐regulating the Wnt/β‐catenin pathway and inhibited oxidative stress and cell senescence. In conclusion, iPS ‐ CM effectively enhanced the cell viability of H9C2 cardiomyocytes and could potentially be used to inhibit cardiomyocytes apoptosis to treat myocardial infarction in the future.

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“…The stimulating proliferation and anti-apoptosis from iPS-CM were the result of cytokines secretion, which were generally safe and would not produce tumours. [19][20][21] The Wnt/b-catenin signalling pathway is the classic pathway involved in cell proliferation. 22 Basic fibroblast growth factor (bFGF) could promote the proliferation and migration of fibroblasts through the activation of Wnt/b-catenin signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway

Chen

Hong

Chen

et al. 2018

J Cellular Molecular Medi

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Leydig cell transplantation is a better alternative in the treatment of androgen‐deficient males. The main purpose of this study was to investigate the effects of induced pluripotent stem cell‐derived conditioned medium (iPS‐CM) on the anti‐apoptosis, proliferation and function of immature Leydig cells (ILCs), and illuminate the underlying mechanisms. ILCs were exposed to 200 μmol/L hydrogen peroxide (H2O2) for 24 hours with or without iPS‐CM treatments. Cell apoptosis was detected by flow cytometric analysis. Cell proliferation was assessed using cell cycle assays and EdU staining. The steroidogenic enzyme expressions were quantified with Western blotting. The results showed that iPS‐CM significantly reduced H2O2‐induced ILC apoptosis through down‐regulation of autophagic and apoptotic proteins LC3‐I/II, Beclin‐1, P62, P53 and BAX as well as up‐regulation of BCL‐2, which could be inhibited by LY294002 (25 μmol/L). iPS‐CM could also promote ILC proliferation through up‐regulation of β‐catenin and its target proteins cyclin D1, c‐Myc and survivin, but was inhibited by XAV939 (10 μmol/L). The level of bFGF in iPS‐CM was higher than that of DMEM‐LG. Exogenous bFGF (20 ng/mL) or Wnt signalling agonist lithium chloride (LiCl) (20 mmol/L) added into DMEM‐LG could achieve the similar effects of iPS‐CM. Meanwhile, iPS‐CM could improve the medium testosterone levels and up‐regulation of LHCGR, SCARB1, STAR, CYP11A1, HSD3B1, CYP17A1, HSD17B3 and SF‐1 in H2O2‐induced ILCs. In conclusion, iPS‐CM could reduce H2O2‐induced ILC apoptosis through the activation of autophagy, promote proliferation through up‐regulation of Wnt/β‐catenin pathway and enhance testosterone production through increasing steroidogenic enzyme expressions, which might be used in regenerative medicine for future.

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

Cited by 19 publications

References 39 publications

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

Induced pluripotent stem cell‐conditional medium inhibits H9C2 cardiomyocytes apoptosis via autophagy flux and Wnt/β‐catenin pathway

Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway

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