Genome-wide transcriptome profiling of human trabecular meshwork cells treated with TGF-β2.
Genome-wide transcriptome profiling of human trabecular meshwork cells treated with TGF-β2.
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DOI：
10.1038/s41598-022-13573-8
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发表时间：
2022-06-10
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
青光眼是一种复杂的神经退行性疾病，导致进行性视神经病变，是世界范围内不可逆失明的主要原因。原发性开角型青光眼（POAG）是影响全球6550万人的主要形式。尽管POAG的患病率和超过120个青光眼相关基因位点的鉴定，其潜在的分子机制仍然知之甚少。转化生长因子β (TGF-β)信号通路与POAG的分子病理有关。为了更好地了解TGF-β2在青光眼小梁网分子病理变化中的作用，我们采用RNA-Seq方法描述了TGF-β2诱导正常原代人小梁网细胞（HTM）转录组的变化。我们发现了大量的差异表达基因和相关途径，这些基因和途径与POAG的发病机制有关。差异表达基因主要富集于ECM调控、TGF-β信号、增殖/凋亡、炎症/伤口愈合、MAPK信号、氧化应激和RHO信号。典型通路分析证实，HTM细胞中RhoA信号、炎症相关过程、ECM和细胞骨架组织在响应TGF-β2时富集。我们还发现了TGF-β2处理后HTM中受影响的新基因和途径，表明其他途径被激活，包括Nrf2， PI3K-Akt， MAPK和HIPPO信号通路。HTM细胞中TGF-β2依赖性差异表达基因和通路的鉴定和表征，对于了解青光眼的病理生理和开发新的治疗药物具有重要意义。
Glaucoma is a complex neurodegenerative disease resulting in progressive optic neuropathy and is a leading cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is the predominant form affecting 65.5 million people globally. Despite the prevalence of POAG and the identification of over 120 glaucoma related genetic loci, the underlaying molecular mechanisms are still poorly understood. The transforming growth factor beta (TGF-β) signalling pathway is implicated in the molecular pathology of POAG. To gain a better understanding of the role TGF-β2 plays in the glaucomatous changes to the molecular pathology in the trabecular meshwork, we employed RNA-Seq to delineate the TGF-β2 induced changes in the transcriptome of normal primary human trabecular meshwork cells (HTM). We identified a significant number of differentially expressed genes and associated pathways that contribute to the pathogenesis of POAG. The differentially expressed genes were predominantly enriched in ECM regulation, TGF-β signalling, proliferation/apoptosis, inflammation/wound healing, MAPK signalling, oxidative stress and RHO signalling. Canonical pathway analysis confirmed the enrichment of RhoA signalling, inflammatory-related processes, ECM and cytoskeletal organisation in HTM cells in response to TGF-β2. We also identified novel genes and pathways that were affected after TGF-β2 treatment in the HTM, suggesting additional pathways are activated, including Nrf2, PI3K-Akt, MAPK and HIPPO signalling pathways. The identification and characterisation of TGF-β2 dependent differentially expressed genes and pathways in HTM cells is essential to understand the patho-physiology of glaucoma and to develop new therapeutic agents.
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影响因子：
3.4
作者：
Flügel-Koch, C;Ohlmann, A;Tamm, ER
通讯作者：
Tamm, ER
影响因子：
3.4
作者：
Alqawlaq, Samih;Flanagan, John G.;Sivak, Jeremy M.
通讯作者：
Sivak, Jeremy M.
影响因子：
4.4
作者：
Fuchshofer, Rudolf;Yu, Alice H. L.;Tamm, Ernst R.
通讯作者：
Tamm, Ernst R.
影响因子：
15.9
作者：
Daehn, Ilse;Casalena, Gabriella;Bottinger, Erwin P.
通讯作者：
Bottinger, Erwin P.
DOI：
10.1016/s2214-109x(20)30425-3
发表时间：
2021-03
期刊：
The Lancet. Global health
影响因子：
--
作者：
GBD 2019 Blindness and Vision Impairment Collaborators;Vision Loss Expert Group of the Global Burden of Disease Study
通讯作者：
Vision Loss Expert Group of the Global Burden of Disease Study