Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice.
Different Effects of Pro-Inflammatory Factors and Hyperosmotic Stress on Corneal Epithelial Stem/Progenitor Cells and Wound Healing in Mice.
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DOI：
10.1002/sctm.18-0005
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发表时间：
2019-01
影响因子：
6
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Yang L;Zhang S;Duan H;Dong M;Hu X;Zhang Z;Wang Y;Zhang X;Shi W;Zhou Q
慢性炎症和严重干眼症是培养的角膜缘干细胞移植成功的两个重要不利因素。本研究的目的是探讨炎症和高渗应激（干眼症的关键病理因素）对角膜上皮干细胞（CESC）和角膜上皮伤口愈合的影响。我们观察到，当用白介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）或高渗应激处理时，CESC 表现出显着的形态变化。集落形成效率或集落形成大小随着IL-1β、TNF-α或高渗应激浓度的增加而降低，当同时使用促炎因子和高渗应激时，这种情况会加剧。然而，促炎因子治疗比高渗应激治疗更容易恢复 CESC 的集落形成能力。此外，与促炎因子治疗相比，高渗应激治疗导致凋亡和坏死细胞数量更显着增加，细胞周期停滞在G2/M期。此外，小鼠模型中角膜上皮伤口愈合的正常能力受到促炎因子和高渗应激治疗的抑制，尤其是高渗应激治疗的抑制。此外，炎症联合高渗应激治疗导致角膜上皮更严重的上皮修复延迟和细胞凋亡。在高渗应激处理的细胞和小鼠角膜中发现炎症因子水平升高，甚至在恢复期间也持续存在。结果表明，促炎因子会导致短暂的抑制，而高渗应激会导致严重的细胞凋亡和坏死、CESCs持续的细胞周期停滞以及严重的角膜伤口愈合延迟。干细胞转化医学2019；8：46–57
Chronic inflammation and severe dry eye are two important adverse factors for the successful transplant of cultured limbal stem cells. The aim of this study was to investigate the effects of inflammation and hyperosmotic stress (a key pathological factor in dry eye) on corneal epithelial stem cells (CESCs) and corneal epithelial wound healing. We observed that the CESCs exhibited significant morphological changes when treated with interleukin‐1 beta (IL‐1β), tumor necrosis factor alpha (TNF‐α), or hyperosmotic stress. Colony‐forming efficiency or colony‐forming size was decreased with the increasing concentrations of IL‐1β, TNF‐α, or hyperosmotic stress, which was exacerbated when treated simultaneously with pro‐inflammatory factors and hyperosmotic stress. However, the colony‐forming capacity of CESCs recovered more easily from pro‐inflammatory factor treatment than from hyperosmotic stress treatment. Moreover, when compared with pro‐inflammatory factors treatment, hyperosmotic stress treatment caused a more significant increase of apoptotic and necrotic cell numbers and cell cycle arrest in the G2/M phase. Furthermore, the normal ability of corneal epithelial wound healing in the mice model was suppressed by both pro‐inflammatory factors and hyperosmotic stress treatment, and especially severely by hyperosmotic stress treatment. In addition, inflammation combined with hyperosmotic stress treatment induced more serious epithelial repair delays and apoptosis in corneal epithelium. Elevated levels of inflammatory factors were found in hyperosmotic stress‐treated cells and mice corneas, which persisted even during the recovery period. The results suggested that pro‐inflammatory factors cause transient inhibition, while hyperosmotic stress causes severe apoptosis and necrosis, persistent cell cycle arrest of CESCs, and severe corneal wound healing delay. Stem Cells Translational Medicine 2019;8:46–57
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影响因子：
4.2
作者：
Basu, Sayan;Ali, Md Hasnat;Sangwan, Virender S.
通讯作者：
Sangwan, Virender S.
影响因子：
4.3
作者：
Haagdorens M;Van Acker SI;Van Gerwen V;Ní Dhubhghaill S;Koppen C;Tassignon MJ;Zakaria N
通讯作者：
Zakaria N
影响因子：
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作者：
Biber, Joseph M;Holland, Edward J;Neff, Kristiana D
通讯作者：
Neff, Kristiana D
影响因子：
2.4
作者：
Bhatia, M.
通讯作者：
Bhatia, M.
影响因子：
4.4
作者：
Crnej, Alja;Omoto, Masahiro;Dana, Reza
通讯作者：
Dana, Reza