Lysozyme promotes renal fibrosis through JAK/STAT3 signal pathway in diabetic nephropathy

Introduction Diabetic nephropathy (DN) is a major reason that could lead to kidney failure. Lysozyme (LYZ) is a part of innate immunity and has been shown to have an antibacterial function. In addition, lysozyme (LYZ) has been reported to be capable of inducing nephropathy, implying a possible association between impaired renal function and lysozyme expression. Material and methods A mouse model of streptozotocin-induced diabetic nephropathy mice model was used to investigate the correlation between DN and LYZ expression, the function of LYZ was confirmed by knockdown and overexpression of LYZ in vivo, and we used immunohistochemistry (IHC) to assess fibrosis-related marker and fibrosis-related cytokine, Masson staining was used to assess renal fibrosis, CCK-8 was used to assess fibroblast proliferation of fibroblasts, the JAK inhibitor AG490 was used to confirm the role played by JAK in this effect, Western-blot was used to investigate the underlying mechanisms. Results Mechanistically, 25 nM glucose promotes the expression of LYZ in fibroblastic cells, and LYZ may in turn promote the proliferation of renal interstitial fibroblasts. Western blot shows that glucose can activate STAT3 in an LYZ-dependent manner, and JAK inhibitor AG490 can partially suppress LYZ-induced STAT3 activation. Furthermore, we have observed that overexpression of LYZ is associated with the senescent phenotype of renal tubular epithelial cells (RTECs) in vivo. Conclusions Lysozyme promotes kidney fibrosis via the JAK/STAT3 signaling pathway in diabetic nephropathy, and glucose may promote fibroblast proliferation by promoting LYZ auto-secretion.