Renal tubular epithelial cells treated with calcium oxalate up-regulate S۱۰۰A۸ and S۱۰۰A۹ expression in M۱-polarized macrophages via interleukin ۶

Objective(s): Calgranulins S۱۰۰A۸ and S۱۰۰A۹ are common in renal stones and they are up-regulated in both urinary exosomes and kidneys of stone patients. Renal sources and important regulators for S۱۰۰A۸ and S۱۰۰A۹ in nephrolithiasis were explored in this study.Materials and Methods: We identified S۱۰۰A۸ and S۱۰۰A۹ abundance in various renal cells by searching the Single Cell Type Atlas. Macrophages were polarized from human myeloid leukemia mononuclear cells. Human proximal renal tubular epithelial cells (HK-۲) were stimulated with calcium oxalate monohydrate (COM). Coculture experiments involving HK-۲ cells and macrophages were conducted. qPCR, Western blotting, ELISA, and immunofluorescence were used for detecting interleukin ۶ (IL۶), S۱۰۰A۸, and S۱۰۰A۹.Results: The Single Cell Type Atlas showed that S۱۰۰A۸ and S۱۰۰A۹ in human kidneys primarily originated from macrophages. M۱ was the predominant macrophage type expressing S۱۰۰A۸ and S۱۰۰A۹. Direct culture with COM did not affect the expression of these two calgranulins in M۱ macrophages but coculture with COM-treated HK-۲ cells did. COM could promote HK-۲ cells to secrete IL۶. IL۶ could up-regulate S۱۰۰A۸ and S۱۰۰A۹ expression in macrophages of M۱ type. In addition, ۰.۵ μM SC۱۴۴ (a kind of IL۶ inhibitor) significantly prevented COM-treated HK-۲ cells from up-regulating S۱۰۰A۸ and S۱۰۰A۹ expression in macrophages of M۱ type.Conclusion: M۱-polarized macrophages were the predominant cell type expressing S۱۰۰A۸ and S۱۰۰A۹ in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL۶ to up-regulate S۱۰۰A۸ and S۱۰۰A۹ expression in macrophages of M۱ type.

کلیدواژه ها:

Calcium oxalate ، Interleukin ۶ ، nephrolithiasis ، S۱۰۰A۸ protein ، S۱۰۰A۹ protein