下调和上调
炎症
促炎细胞因子
转录组
HMOX1型
CXCL1型
肌成纤维细胞
白内障手术
免疫学
眼科
转化生长因子
S100A9型
生物
医学
纤维化
病理
细胞生物学
趋化因子
基因表达
基因
血红素加氧酶
遗传学
血红素
酶
生物化学
作者
Jian Jiang,Mahbubul H. Shihan,Yan Wang,Melinda K. Duncan
标识
DOI:10.1167/iovs.18-25067
摘要
Lens epithelial cell (LEC) conversion to myofibroblast is responsible for fibrotic cataract surgery complications including posterior capsular opacification. While transforming growth factor beta (TGFβ) signaling is important, the mechanisms by which the TGFβ pathway is activated post cataract surgery (PCS) are not well understood.RNA-seq was performed on LECs obtained from a mouse cataract surgery model at the time of surgery and 24 hours later. Bioinformatic analysis was performed with iPathwayGuide. Expression dynamics were determined by immunofluorescence.The LEC transcriptome is massively altered by 24 hours PCS. The differentially expressed genes included those important for lens biology, and fibrotic markers. However, the most dramatic changes were in the expression of genes regulating the innate immune response, with the top three altered genes exhibiting greater than 1000-fold upregulation. Immunolocalization revealed that CXCL1, S100a9, CSF3, COX-2, CCL2, LCN2, and HMOX1 protein levels upregulate in LECs between 1 hour and 6 hours PCS and peak at 24 hours PCS, while their levels sharply attenuate by 3 days PCS. This massive upregulation of known inflammatory mediators precedes the infiltration of neutrophils into the eye at 18 hours PCS, the upregulation of canonical TGFβ signaling at 48 hours PCS, and the infiltration of macrophages at 3 days PCS.These data demonstrate that LECs produce proinflammatory cytokines immediately following lens injury that could drive postsurgical flare, and suggest that inflammation may be a major player in the onset of lens-associated fibrotic disease PCS.
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