Macrophage-derived exosomes from high-glucose stimulated cells promote glomerular fibrosis via NF-κB/TGF-β1 signaling pathway
SONG Hui-jie
LI Yang
TAN Yi
HE Xu-mei
Abstract：Objective To investigate whether exosomes(Exos)derived from macrophages under high glucose(HG)conditions can activate glomerular mesangial cells and promote the production of pro-fibrotic cytokines,and to ex-plore whether this effect is related to the activation of the nuclear factor kappa-B(NF-κB)/transforming growth factor-β1(TGF-β1)signaling pathway.Methods Exosomes from high glucose-treated Raw264.7 cells(HG-Exos)were incubated with SV40MES13 cells for 24 hours.The effects of Exos on SV40MES13 cell proliferation and apoptosis were as-sessed using EdU and TUNEL assays.ELISA was used to measure the levels of extracellular matrix(ECM)components[Collagen Type Ⅳ(Col Ⅳ)and fibronectin(FN)]in the supernatant.Quantitative RT-PCR was used to analyze the expression of TGF-β1 mRNA,and Western blotting was performed to detect the protein levels of NF-κB/TGF-β1/Smad3 signaling pathway components.Results Compared to NG-Exos,HG-Exos significantly increased the secretion of Col Ⅳ,FN,and TGF-β1 mRNA in SV40MES13 cells(P＜0.05).Western blot analysis confirmed that TGF-β1,Smad3,p-Smad3,NF-κB p65,and p-NF-κB p65 protein levels were significantly higher in SV40MES13 cells trea-ted with HG-Exos compared to NG-Exos(P＜0.05).Co-treatment with PDTC(an NF-κB specific inhibitor)and HG-Exos for 24 hours significantly reduced the levels of Col Ⅳ,FN,TGF-β1,Smad3,and p-Smad3 proteins com-pared to HG-Exos treatment alone.Conclusion High glucose-treated macrophage-derived exosomes may promote glomerular fibrosis by activating glomerular mesangial cells through the NF-κB/TGF-β1 signaling pathway.
Keywords：high glucosemacrophagesexosomesrenal fibrosisNF-κB/TGF-β1 signal
Publication Date：2024-11-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1391-1396 )