Abstract
BackgroundRenal fibrosis is inevitable in all progressive chronic kidney diseases (CKDs) and represents a serious public health problem. Immune factors contribute to the progression of renal fibrosis. Thus, it is very possible that immunosuppression cells, such as myeloid-derived suppressor cells (MDSCs), could bring benefits to renal fibrosis. Herein, this study investigated the antifibrotic and reno-protective effect of MDSCs and the possible mechanisms.MethodsMurine and cell models of unilateral ureter obstruction (UUO) renal fibrosis were used. Bone marrow-induced MDSCs and granulocyte–macrophage colony-stimulating factor (GM-CSF) were pretreated before surgery. Kidney weight, pathological injury, extracellular matrix deposition, and epithelial–mesenchymal transition progression were examined. Transforming growth factor (TGF)-β1)/Smad/Snail signaling pathway involvement was investigated through Western blotting and quantitative PCR (qPCR). Accumulation of MDSC, CD4+ T cell, regulatory T (Treg), and T helper 1 (TH1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry.ResultsIn vitro- and in vivo-induced MDSCs significantly ameliorated UUO-induced tubulointerstitial fibrosis, inhibited the TGF-β1/Smad/Snail signaling pathway, and enhanced MDSC and Treg infiltration in the kidney while downregulating the TH1 cells. Both in vitro and in vivo experiments confirmed CCL5 elevation in the two MDSC-treated groups.Conclusion In vitro- and in vivo-induced MDSCs alleviated renal fibrosis similarly through promoting the CCL5–CCR5 axis interaction and TGF-β1/Smad/Snail signaling pathway inhibition. Our results indicate an alternative treatment for renal fibrosis.
Highlights
Renal fibrosis is the common outcome of all progressive chronic kidney diseases (CKDs), which brings a great burden to public health [1]
The kidney weight significantly decreased on the ligation side, and the pelvis and calices were severely dilated with atrophied renal parenchyma in the ureter obstruction (UUO) group (Figure 1B)
Kidney weight increased in the myeloid-derived suppressor cells (MDSCs) or granulocyte–macrophage colony stimulating factor (GM-CSF) groups (Figure 1B), and renal fibrosis injury was significantly alleviated (Figure 1C)
Summary
Renal fibrosis is the common outcome of all progressive chronic kidney diseases (CKDs), which brings a great burden to public health [1]. Adoptive transference of MDSCs have an excellent performance in autoimmune disease treatment and allograft protection [9,10,11]. Their treating effects have been confirmed in acute renal injury and chronic renal fibrosis [12]. Renal fibrosis is inevitable in all progressive chronic kidney diseases (CKDs) and represents a serious public health problem. It is very possible that immunosuppression cells, such as myeloid-derived suppressor cells (MDSCs), could bring benefits to renal fibrosis. This study investigated the antifibrotic and reno-protective effect of MDSCs and the possible mechanisms
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