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Proteomics analysis and proteogenomic characterization of different physiopathological human lenses.

ABSTRACT: The 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.The 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.The 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.These 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.

SUBMITTER: Wu X

PROVIDER: S-EPMC5735820 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Proteomics analysis and proteogenomic characterization of different physiopathological human lenses.

Wu Xiaohang X Liu Zhenzhen Z Zhang Xiayin X Wang Dongni D Long Erping E Wang Jinghui J Li Wangting W Lai Weiyi W Cao Qianzhong Q Hu Kunhua K Chen Weirong W Lin Haotian H Liu Yizhi Y

BMC ophthalmology 20171219 1

<h4>Background</h4>The 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.<h4>Methods</h4>The 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 q ...[more]

PMID: 29258473

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Project description:PurposeThe goal of this study was to identify and quantify the differentially expressed proteins in human nuclear cataract with different axial lengths.MethodsThirty-six samples of human lens nuclei with hardness grade III or IV were obtained during cataract surgery with extracapsular cataract extraction (ECCE). Six healthy transparent human lens nuclei were obtained from fresh healthy cadaver eyes during corneal transplantation surgery. The lens nuclei were divided into seven groups (six lenses in each group) according to the optic axis: Group A (mean axial length 28.7±1.5 mm; average age 59.8±1.9 years), Group B (mean axial length 23.0±0.4 mm; average age 60.3±2.5 years), Group C (mean axial length 19.9±0.5 mm; average age 55.1±2.5 years), Group D (mean axial length 28.7±1.4 mm; average age 58.0±4.0 years), Group E (mean axial length 23.0±0.3 mm; average age 56.9±4.2 years), and Group F (mean axial length 20.7±0.6 mm; average age 57.6±5.3 years). The six healthy transparent human lenses were included in a younger group with standard optic axes, Group G (mean axial length 23.0±0.5 mm; average age 34.7±4.2 years).Water-soluble, water-insoluble, and water-insoluble-urea-soluble protein fractions were extracted from the samples. The three-part protein fractions from the individual lenses were combined to form the total proteins of each sample. The proteomic profiles of each group were analyzed using 8-plex isobaric tagging for relative and absolute protein quantification (iTRAQ) labeling combined with two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS). The data were analyzed with ProteinPilot software for peptide matching, protein identification, and quantification. Differentially expressed proteins were validated with western blotting.ResultsWe employed biological and technical replicates and selected the intersection of the two sets of results, which included 40 proteins. From the 40 proteins identified, six were selected as differentially expressed proteins closely related to axial length. The six proteins were gap junction alpha-3 protein, beta-crystallin B2, T-complex protein 1 subunit beta, gamma-enolase, pyruvate kinase isozymes M1/M2, and sorbitol dehydrogenase. Levels of beta-crystallin B2 expression were decreased in nuclear cataracts with longer axial length. The results of the mass spectrometric analysis were consistent with the western blot validation.ConclusionThe discovery of these differentially expressed proteins provides valuable clues for understanding the pathogenesis of axial-related nuclear cataract. The results indicate that beta-crystallin B2 (CRBB2) may be involved in axial-related nuclear cataract pathogenesis. Further studies are needed to investigate the correlation between CRBB2 and axial-related nuclear cataract.

Dataset Information

Proteomics analysis and proteogenomic characterization of different physiopathological human lenses.

Publications

Proteomics analysis and proteogenomic characterization of different physiopathological human lenses.

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