Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB.
OBJECTIVE
This study aimed to evaluate the molecular mechanism mitigating progress of chronic nephropathy by mesenchymal stem cells (MSCs).


METHODS
Rats were divided into normal control (Normal), adriamycin (ADR)+vehicle (CON), and ADR+MSC (MSC) groups. Nephropathy was induced by ADR (4 mg/kg) and MSCs (2 × 106) were injected. Rats were euthanized 1 or 6 weeks after ADR injection. NF-kB, MAPKs, inflammation, oxidative stress, profibrotic molecules, and nephrin expression were evaluated. Electron and light microscopy were used for structural analysis. MSCs were co-cultured with renal tubular epithelial cells or splenocytes to evaluate relation with oxidative stress and inflammatory molecules RESULTS: Adriamycin treatment upregulated inflammation, oxidative stress, and profibrotic molecules; this was mitigated by MSCs. Glomerulosclerosis and interstitial fibrosis were observed in ADR-treated groups, and were more prominent in the CON group than in the MSC group. Fusion of foot processes and loss of slit diaphragms were also more prominent in the CON group than in the MSC group. In vitro, MSCs reduced oxidative stress related molecules, inflammatory cytokines, and NF-kB transcription. MSC- or ADR-induced regulation of NF-kB transcriptional activity was confirmed by a luciferase reporter assay.


CONCLUSIONS
Mesenchymal stem cells attenuate ADR-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of NF-kB.
Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea.
In-Hwan
IH
Song
Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea.
Kyong-Jin
KJ
Jung
Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea.
Tae-Jin
TJ
Lee
Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea.
Joo-Young
JY
Kim
Department of Anatomy, Yeungnam University College of Medicine, Daegu, South Korea.
Eon-Gi
EG
Sung
Pediatrics, Yeungnam University College of Medicine, Daegu, South Korea.
Young Chul
YC
Bae
Department of Anatomy, Kyungpook National University School of Dentistry, Daegu, South Korea.
Yong Hoon
YH
Park
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004317:Doxorubicin; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors
D018836:Inflammation Mediators; D016328:NF-kappa B; D004317:Doxorubicin
NF-kB; adriamycin; inflammation; mesenchymal stem cells; nephropathy; oxidative; stress