Selected renal cells modulate disease progression in rodent models of chronic kidney disease via NF-κB and TGF-β1 pathways
| Autor: | Sumana Choudhury, Timothy A. Bertram, Andrew T Bruce, Thomas Spencer, Joydeep Basu, Elias Rivera, Deepak Jain, Russell W. Kelley, Namrata Sangha, Roger M. Ilagan, Kelly I. Guthrie |
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| Rok vydání: | 2015 |
| Předmět: |
Embryology
Cell Biomedical Engineering Biology Cell therapy Transforming Growth Factor beta1 Paracrine signalling In vivo Plasminogen Activator Inhibitor 1 medicine Animals Renal Insufficiency Chronic Kidney Macrophages NF-kappa B Cell cycle Rats Rats Zucker Disease Models Animal medicine.anatomical_structure Kidney Tubules Gene Expression Regulation Immunology Cancer research Stem cell Rats Transgenic Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Regenerative medicine. 10(7) |
| ISSN: | 1746-076X |
| Popis: | Aim: Identification of mechanistic pathways for selected renal cell (SRC) therapeutic bioactivity in rodent models of chronic kidney disease. Materials & methods: In vivo and in vitro functional bioassays applied to investigate regenerative outcomes associated with delivery of SRC to diseased rodent kidney. Results: In vivo, SRC reduces chronic infiltration by monocytes/macrophages. SRC attenuates NF-κB and PAI-1 responses while simultaneously promoting host tubular cell expansion through trophic cues. In vitro, SRC-derived conditioned media attenuates TNF-α-induced NF-κB response, TGF-β-mediated PAI-1 response and increases expression of transcripts associated with cell cycle regulation. Observed bioactive responses were from vesicle and nonvesicle-associated factors, including specific miRNAs. Conclusion: We identify a paracrine mechanism for SRC immunomodulatory and trophic cues on host renal tissues, catalyzing long-term functional benefits in vivo. |
| Databáze: | OpenAIRE |
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