Premium
Umbilical cord stromal cell (UCSC) exosomes protect tubular epithelial cells from gentamicin injury
Author(s) -
Borges Fernanda Teixeira,
Novaes Antonio,
Schor Nestor
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.748.2
Subject(s) - microvesicles , mesenchymal stem cell , stromal cell , paracrine signalling , microbiology and biotechnology , chemistry , exosome , bone marrow , biology , microrna , cancer research , immunology , biochemistry , gene , receptor
Bone Marrow Mesenchymal Stromal Cells (MSCs) and Umbilical Cord Stromal Cells (UCSC) protect the kidney against nephrotoxic insults. This effect could be paracrine, possibly mediated by extracellular vesicles. Exosomes (EXOs) are extracellular vesicles that transfer mRNA and microRNA to the recipient cells, mediating the communication between them. Mir 126 mediates the protective effect of stem cell microvesicles. The goal of the present study was to analyze the effects of EXOs from MSCs and UCSC on proximal tubular epithelial cells from rats (RPTC) exposed to gentamicin (genta). UCSC and MSCs were maintained in culture conditions and every 3 days the culture medium was collected. EXOs were extracted through filtration in the 0.1μm filter, followed by ultracentrifugation (100,000g during 2h). Mir 126 from stromal cells and EXOs were extracted and analyzed by real time‐PCR. RPTC cells were exposed to gentamicin (2mM) in the presence or absence of exosomes (50 μg/ml), DNA damage and proliferation was analyzed by H2Ax and BrDU immunofluorescence, respectively. The expression of p21 and c‐myc was analyzed in RPTC through western blot. Mir 126 expression was increased in exosomes in comparison to stromal cells. It was increased in BM‐MSC exosomes (2.52 ± 0.12 AU) in comparison to UCSC exosomes (1.2 ± 0.2 AU). The treatment with UCSC‐EXO, but not with MSC‐EXO, stimulated the proliferation and decreased DNA damage induced by gentamicin in tubular cells. MSC‐EXO increased proliferation and decreased DNA damage when mir126 was depleted from exosomes with 126 antimir. RPTC cells treated with UCSC‐EXO increased the tumor suppressor protein p21 and increased in cell cycle progress protein c‐myc. MSC‐EXO did not show the same effect. Our results suggest that stromal cell exosomes carry mir 126 and this microRNA could be related to the paracrine protective effect of umbilical stromal cell exosome. Support or Funding Information Supported by FAPESP, CNPq, CAPES and FOR