Proteomic analysis of corneal endothelial cell-descemet membrane tissues reveals influence of insulin dependence and disease severity in type 2 diabetes mellitus

Autor: Cynthia R. Reed, Andrew S. Goldstein, Jessica M. Skeie, Gregory A. Schmidt, Mark A. Greiner, Benjamin T. Aldrich
Rok vydání: 2018
Předmět:
Proteomics
0301 basic medicine
Pulmonology
Proteome
Protein Expression
lcsh:Medicine
Mitochondrion
Pathology and Laboratory Medicine
Biochemistry
Epithelium
Cornea
Endocrinology
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Human proteome project
Insulin
lcsh:Science
Energy-Producing Organelles
Multidisciplinary
Endothelium
Corneal
Middle Aged
Mitochondria
Cell biology
medicine.anatomical_structure
Anatomy
Cellular Structures and Organelles
Cellular Types
Signal transduction
Research Article
Signal Transduction
Corneal endothelium
Endocrine Disorders
Ocular Anatomy
Chronic Obstructive Pulmonary Disease
Pain
Bioenergetics
Biology
Research and Analysis Methods
03 medical and health sciences
Signs and Symptoms
Ocular System
Diagnostic Medicine
Diabetes mellitus
Diabetes Mellitus
Gene Expression and Vector Techniques
medicine
Humans
Molecular Biology Techniques
Molecular Biology
Descemet Membrane
Neuropathic Pain
Aged
Diabetic Endocrinology
Basement membrane
Molecular Biology Assays and Analysis Techniques
lcsh:R
Biology and Life Sciences
Endothelial Cells
Type 2 Diabetes Mellitus
Epithelial Cells
Cell Biology
medicine.disease
Hormones
eye diseases
Biological Tissue
030104 developmental biology
Diabetes Mellitus
Type 2
Metabolic Disorders
030221 ophthalmology & optometry
lcsh:Q
sense organs
Zdroj: PLoS ONE, Vol 13, Iss 3, p e0192287 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: The objective of this study was to characterize the proteome of the corneal endothelial cell layer and its basement membrane (Descemet membrane) in humans with various severities of type II diabetes mellitus compared to controls, and identify differentially expressed proteins across a range of diabetic disease severities that may influence corneal endothelial cell health. Endothelium-Descemet membrane complex tissues were peeled from transplant suitable donor corneas. Protein fractions were isolated from each sample and subjected to multidimensional liquid chromatography and tandem mass spectrometry. Peptide spectra were matched to the human proteome, assigned gene ontology, and grouped into protein signaling pathways unique to each of the disease states. We identified an average of 12,472 unique proteins in each of the endothelium-Descemet membrane complex tissue samples. There were 2,409 differentially expressed protein isoforms that included previously known risk factors for type II diabetes mellitus related to metabolic processes, oxidative stress, and inflammation. Gene ontology analysis demonstrated that diabetes progression has many protein footprints related to metabolic processes, binding, and catalysis. The most represented pathways involved in diabetes progression included mitochondrial dysfunction, cell-cell junction structure, and protein synthesis regulation. This proteomic dataset identifies novel corneal endothelial cell and Descemet membrane protein expression in various stages of diabetic disease. These findings give insight into the mechanisms involved in diabetes progression relevant to the corneal endothelium and its basement membrane, prioritize new pathways for therapeutic targeting, and provide insight into potential biomarkers for determining the health of this tissue.
Databáze: OpenAIRE
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