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Mechanisms of kidney repair by human mesenchymal stromal cells after ischemia: A comprehensive view using label‐free MS E
Author(s) -
Costa Milene R.,
Pizzatti Luciana,
Lindoso Rafael S.,
Sant’Anna Julliana Ferreira,
DuRocher Barbara,
Abdelhay Eliana,
Vieyra Adalberto
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300084
Subject(s) - mesenchymal stem cell , paracrine signalling , microbiology and biotechnology , stromal cell , renal ischemia , apoptosis , signal transduction , acute kidney injury , biology , kidney , cell , blot , intracellular , chemistry , ischemia , cancer research , medicine , reperfusion injury , biochemistry , receptor , endocrinology , gene
Acute kidney injury ( AKI ) is one of the more frequent and lethal pathological conditions seen in intensive care units. Currently available treatments are not totally effective but stem cell‐based therapies are emerging as promising alternatives, especially the use of mesenchymal stromal cells ( MSC ), although the signaling pathways involved in their beneficial actions are not fully understood. The objective of this study was to identify signaling networks and key proteins involved in the repair of ischemia by MSC . Using an in vitro model of AKI to investigate paracrine interactions and label‐free high definition 2D‐Nano ESI ‐ MS E , differentially expressed proteins were identified in a human renal proximal tubule cell lineage ( HK ‐2) exposed to human MSC (h MSC ) after an ischemic insult. In silico analysis showed that h MSC stimulated antiapoptotic activity, normal ROS handling, energy production, cytoskeleton organization, protein synthesis, and cell proliferation. The proteomic data were validated by parallel experiments demonstrating reduced apoptosis in HK ‐2 cells and recovery of intracellular ATP levels. q RT ‐ PCR for proteins implicated in the above processes revealed that h MSC exerted their effects by stimulating translation, not transcription. Western blotting of proteins associated with ROS and energy metabolism confirmed their higher abundance in HK ‐2 cells exposed to h MSC .