Sang Tian, Wang Yani, Wang Zhiqing, Sun Di, Dou Shengqian, Yu Yaoyao, Wang Xiaoyun, Zhao Can, Wang Qun
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, China.
School of Clinical Medicine, Weifang Medical University, Shandong, China.
Invest Ophthalmol Vis Sci. 2024 Mar 5;65(3):10. doi: 10.1167/iovs.65.3.10.
This study aimed to investigate the role of the long non-coding RNA (lncRNA) NEAT1 in corneal epithelial wound healing in mice.
The central corneal epithelium of wild-type (WT), MALAT1 knockout (M-KO), NEAT1 knockout (N-KO), and NEAT1 knockdown (N-KD) mice was scraped to evaluate corneal epithelial and nerve regeneration rates. RNA sequencing of the corneal epithelium from WT and N-KO mice was performed 24 hours after debridement to determine the role of NEAT1. Quantitative PCR (qPCR) and ELISA were used to confirm the bioinformatic analysis. The effects of the cAMP signaling pathway were evaluated in N-KO and N-KD mice using SQ22536, an adenylate cyclase inhibitor.
Central corneal epithelial debridement in N-KO mice significantly promoted epithelial and nerve regeneration rates while suppressing inflammatory cell infiltration. Furthermore, the expression of Atp1a2, Ppp1r1b, Calm4, and Cngb1, which are key components of the cAMP signaling pathway, was upregulated in N-KO mice, indicative of its activation. Furthermore, the cAMP pathway inhibitor SQ22536 reversed the accelerated corneal epithelial wound healing in both N-KO and N-KD mice.
NEAT1 deficiency contributes to epithelial repair during corneal wound healing by activating the cAMP signaling pathway, thereby highlighting a potential therapeutic strategy for corneal epithelial diseases.
本研究旨在探讨长链非编码RNA（lncRNA）NEAT1在小鼠角膜上皮伤口愈合中的作用。
刮除野生型（WT）、MALAT1基因敲除（M-KO）、NEAT1基因敲除（N-KO）和NEAT1基因敲低（N-KD）小鼠的中央角膜上皮，以评估角膜上皮和神经再生率。在清创术后24小时对WT和N-KO小鼠的角膜上皮进行RNA测序，以确定NEAT1的作用。采用定量PCR（qPCR）和酶联免疫吸附测定（ELISA）来证实生物信息学分析结果。使用腺苷酸环化酶抑制剂SQ22536评估N-KO和N-KD小鼠中cAMP信号通路的作用。
N-KO小鼠的中央角膜上皮清创显著促进了上皮和神经再生率，同时抑制了炎性细胞浸润。此外，cAMP信号通路的关键成分Atp1a2、Ppp1r1b、Calm4和Cngb1在N-KO小鼠中的表达上调，表明该信号通路被激活。此外，cAMP通路抑制剂SQ22536逆转了N-KO和N-KD小鼠角膜上皮伤口愈合加速的情况。
NEAT1缺陷通过激活cAMP信号通路促进角膜伤口愈合过程中的上皮修复，从而为角膜上皮疾病突出了一种潜在的治疗策略。
