Quantification of molecular heterogeneity in kidney tissue by targeted proteomics

Publication date: Available online 6 March 2018
Source:Journal of Proteomics
Author(s): K. Johanna R. Hoyer, Sebastian Dittrich, Malte P. Bartram, Markus M. Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility. Here, we provide an overview of targeted proteomics studies in renal tissue and their insights into major renal diseases such as diabetic nephropathy, acute kidney injury and chronic kidney disease. The technical approaches range from antibody-based to single-nephron and single-cell proteomic approaches, from physiological studies to translational approaches in biomarker discovery. We identify key challenges in proteomics of kidney biopsies. We also identify novel models of translational nephrology with most need for increased targeted acquisition of proteomics data with focus on primary urinary cells, organoids and induced renal epithelial cells (IRECs).SignificanceImproved targeted proteomics technologies will be an important cornerstone of renal systems medicine, in particular to identify and tackle the heterogenic disease mechanisms driving renal disease.



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