Proteomics analysis and proteogenomic characterization of different physiopathological human lenses

BMC Ophthalmology

Research Article

Kunhua Hu¹  Jinghui Wang²  Qianzhong Cao²  Dongni Wang²  Weirong Chen²  Xiayin Zhang²  Erping Long²  Yizhi Liu²  Wangting Li²  Xiaohang Wu²  Zhenzhen Liu²  Haotian Lin²  Weiyi Lai² 

[1] Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China;State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54# Xianlie Road, 510060, Guangzhou, Guangdong, China;

关键词: Human lens;    Regenerative lenses with secondary cataract (RLSC);    Proteomics;    Proteogenomic analysis;   

DOI  :  10.1186/s12886-017-0642-9

 received in 2017-04-04, accepted in 2017-12-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization.MethodsThe total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ). The up-regulated proteins between the groups were subjected to biological analysis. Whole exome sequencing (WES) was performed to detect genetic variations.ResultsThe most complete human lens proteome to date, which consisted of 1251 proteins, including 55.2% previously unreported proteins, was identified across the experimental groups. Bioinformatics functional annotation revealed the common involvement of cellular metabolic processes, immune responses and protein folding disturbances among the groups. RLSC-over-expressed proteins were characteristically enriched in the intracellular immunological signal transduction pathways. The CC groups featured biological processes relating to gene expression and vascular endothelial growth factor (VEGF) signaling transduction, whereas the molecular functions corresponding to external stress were specific to the ARC groups. Combined with WES, the proteogenomic characterization narrowed the list to 16 candidate causal molecules.ConclusionsThese findings revealed common final pathways with diverse upstream regulation of cataractogenesis in different physiopathological states. This proteogenomic characterization shows translational potential for detecting susceptibility genes/proteins in precision medicine.

【 授权许可】

CC BY   
© The Author(s). 2017