Retinal Proteomic Alterations and Combined Transcriptomic-Proteomic Analysis in the Early Stages of Progression of a Mouse Model of X-Linked Retinoschisis

被引:4
作者
Jin, Xiuxiu [1 ,2 ]
Zhang, Xiaoli [3 ]
Liu, Jingyang [1 ,2 ]
Wang, Weiping [1 ,2 ]
Liu, Meng [3 ]
Yang, Lin [3 ]
Liu, Guangming [1 ]
Qiu, Ruiqi [1 ]
Yang, Mingzhu [1 ]
Yao, Shun [1 ]
Lei, Bo [1 ,2 ,3 ]
机构
[1] Zhengzhou Univ, Henan Eye Hosp, Henan Prov Peoples Hosp, Henan Eye Inst,Peoples Hosp, Zhengzhou 450003, Peoples R China
[2] Henan Prov Peoples Hosp, Branch Natl Clin Res Ctr Ocular Dis, Zhengzhou 450003, Peoples R China
[3] Zhengzhou Univ, Acad Med Sci, Zhengzhou 450001, Peoples R China
基金
中国国家自然科学基金;
关键词
X-linked retinoschisis; proteome; RS1; retina; photoreceptor; MESSENGER-RNA DECAY; B-WAVE; SYNAPTIC PATHOLOGY; CELL-MIGRATION; GENE-THERAPY; EXPRESSION; BIPOLAR; PHOTORECEPTOR; MUTATION; DENSITY;
D O I
10.3390/cells11142150
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
X-linked retinoschisis (XLRS) is among the most commonly inherited degenerative retinopathies. XLRS is caused by functional impairment of RS1. However, the molecular mechanisms underlying RS1 malfunction remain largely uncharacterized. Here, we performed a data-independent acquisition-mass spectrometry-based proteomic analysis in RS1-null mouse retina with different postal days (Ps), including the onset (P15) and early progression stage (P56). Gene set enrichment analysis showed that type I interferon-mediated signaling was upregulated and photoreceptor proteins responsible for detection of light stimuli were downregulated at P15. Positive regulation of Tor signaling was downregulated and nuclear transcribed mRNA catabolic process nonsense-mediated decay was upregulated at P56. Moreover, the differentially expressed proteins at P15 were enriched in metabolism of RNA and RNA destabilization. A broader subcellular localization distribution and enriched proteins in visual perception and phototransduction were evident at P56. Combined transcriptomic-proteomic analysis revealed that functional impairments, including detection of visible light, visual perception, and visual phototransduction, occurred at P21 and continued until P56. Our work provides insights into the molecular mechanisms underlying the onset and progression of an XLRS mouse model during the early stages, thus enhancing the understanding of the mechanism of XLRS.
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页数:18
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