PMID- 26988026 OWN - NLM STAT- MEDLINE DCOM- 20170125 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Mar 18 TI - Unfractionated bone marrow cells attenuate paraquat-induced glomerular injury and acute renal failure by modulating the inflammatory response. PG - 23287 LID - 10.1038/srep23287 [doi] LID - 23287 AB - The aim of this study was to evaluate the efficacy of unfractionated bone marrow cells (BMCs) in attenuating acute kidney injury (AKI) induced by paraquat (PQ) in a mouse model. PQ (55 mg/kg BW) was intraperitoneally injected into C57BL/6 female mice to induce AKI, including renal function failure, glomerular damage and renal tubule injury. Glomerular podocytes were the first target damaged by PQ, which led to glomerular injury. Upon immunofluorescence staining, podocytes depletion was validated and accompanied by increased urinary podocin levels, measured on days 1 and 6. A total of 5.4 x 10(6) BMCs obtained from the same strain of male mice were injected into AKI mice through the tail vein at 3, 24, and 48 hours after PQ administration. As a result, renal function increased, tubular and glomerular injury were ameliorated, podocytes loss improved, and recipient mortality decreased. In addition, BMCs co-treatment decreased the extent of neutrophil infiltration and modulated the inflammatory response by shifting from pro-inflammatory Th1 to an anti-inflammatory Th2 profile, where IL-1beta, TNF-alpha, IL-6 and IFN-gamma levels declined and IL-10 and IL-4 levels increased. The present study provides a platform to investigate PQ-induced AKI and repeated BMCs injection represents an efficient therapeutic strategy. FAU - Gu, Sing-Yi AU - Gu SY AD - Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Yeh, Ti-Yen AU - Yeh TY AD - Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lin, Shih-Yi AU - Lin SY AD - Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Peng, Fu-Chuo AU - Peng FC AD - Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160318 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (NPHS2 protein) RN - PLG39H7695 (Paraquat) SB - IM MH - Acute Kidney Injury/chemically induced/immunology/*therapy MH - Animals MH - Bone Marrow Transplantation/*methods MH - Cells, Cultured MH - Cytokines/*metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation MH - Intracellular Signaling Peptides and Proteins/urine MH - Kidney Glomerulus/immunology/*pathology MH - Membrane Proteins/urine MH - Mice MH - Paraquat/*toxicity MH - Th1 Cells/immunology MH - Th2 Cells/immunology PMC - PMC4796871 EDAT- 2016/03/19 06:00 MHDA- 2017/01/26 06:00 PMCR- 2016/03/18 CRDT- 2016/03/19 06:00 PHST- 2015/11/23 00:00 [received] PHST- 2016/03/03 00:00 [accepted] PHST- 2016/03/19 06:00 [entrez] PHST- 2016/03/19 06:00 [pubmed] PHST- 2017/01/26 06:00 [medline] PHST- 2016/03/18 00:00 [pmc-release] AID - srep23287 [pii] AID - 10.1038/srep23287 [doi] PST - epublish SO - Sci Rep. 2016 Mar 18;6:23287. doi: 10.1038/srep23287.