PMID- 37817516 OWN - NLM STAT- Publisher LR - 20231011 IS - 2212-3946 (Electronic) IS - 1574-888X (Linking) DP - 2023 Oct 4 TI - Mesenchymal Stem Cell-conditioned Medium Protecting Renal Tubular Epithelial Cells by Inhibiting Hypoxia-inducible Factor-1alpha and Nuclear Receptor Coactivator-1. LID - 10.2174/011574888X247652230928064627 [doi] AB - BACKGROUND: Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia. METHODS: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), and hypoxia-inducible factor-1 alpha (HIF-1alpha) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 muM DFO, and 25 muM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 muM DFO were added, and cells were cultured for another 24 hours before analysis. RESULTS: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 muM DFO for 24 hours induced HIF-1alpha and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of alpha-SMA, TGF-beta1, HIF-1alpha and NCoA-1. CONCLUSION: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1alpha and NCoA-1, which may be the harmful factors in renal injury. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Liao, Chunling AU - Liao C AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. FAU - Weng, Wenjuan AU - Weng W AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. FAU - Liu, Yiping AU - Liu Y AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. FAU - Lin, Yongda AU - Lin Y AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. FAU - Wang, Jiali AU - Wang J AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. FAU - Zhou, Tianbiao AU - Zhou T AD - Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China. LA - eng PT - Journal Article DEP - 20231004 PL - United Arab Emirates TA - Curr Stem Cell Res Ther JT - Current stem cell research & therapy JID - 101272517 SB - IM OTO - NOTNLM OT - HIF-1? OT - MSC-conditioned medium (MSC-CM) OT - NCoA-1 OT - acute kidney injury (AKI) OT - deferoxamine (DFO) OT - renal tubular epithelial cells (RTECs) EDAT- 2023/10/11 06:45 MHDA- 2023/10/11 06:45 CRDT- 2023/10/11 02:33 PHST- 2023/02/28 00:00 [received] PHST- 2023/08/09 00:00 [revised] PHST- 2023/08/24 00:00 [accepted] PHST- 2023/10/11 06:45 [medline] PHST- 2023/10/11 06:45 [pubmed] PHST- 2023/10/11 02:33 [entrez] AID - CSCR-EPUB-134759 [pii] AID - 10.2174/011574888X247652230928064627 [doi] PST - aheadofprint SO - Curr Stem Cell Res Ther. 2023 Oct 4. doi: 10.2174/011574888X247652230928064627.