Effects of secretome derived from macrophages exposed to calcium oxalate crystals on renal fibroblast activation

The association between kidney stone disease and renal fibrosis has been widely explored in recent years but its underlying mechanisms remain far from complete understanding. Using label-free quantitative proteomics (nanoLC-ESI-LTQ-Orbitrap MS/MS), this study identified 23 significantly altered secreted proteins from calcium oxalate monohydrate (COM)-exposed macrophages (COM-MP) compared with control macrophages (Ctrl-MP) secretome. Functional annotation and protein-protein interactions network analysis revealed that these altered secreted proteins were involved mainly in inflammatory response and fibroblast activation. BHK-21 renal fibroblasts treated with COM-MP secretome had more spindle-shaped morphology with greater spindle index. Immunofluorescence study and gelatin zymography revealed increased levels of fibroblast activation markers (alpha-smooth muscle actin and F-actin) and fibrotic factors (fibronectin and matrix metalloproteinase-9 and -2) in the COM-MP secretome-treated fibroblasts. Our findings indicate that proteins secreted from macrophages exposed to COM crystals induce renal fibroblast activation and may play important roles in renal fibrogenesis in kidney stone disease. Yoodee et al use label-free quantitative proteomics (nanoLC-ESI-LTQ-Orbitrap MS/MS) to identify 23 significantly altered secreted proteins from calcium oxalate monohydrate (COM)-exposed macrophages secretome. They demonstrate that proteins secreted from macrophages exposed to COM crystals induce renal fibroblast activation and may play important roles in renal fibrogenesis in kidney stone disease.

Automated summary

Using label-free quantitative proteomics, this study identified significantly altered secreted proteins from COM-exposed macrophages, suggesting their potential role in renal fibrogenesis in kidney stone disease.