Authors

Hao Xu*, Jing Zhou**, Shuhong Zhou*, #

Departments

*Department of Rheumatology and Immunology, Gansu Provincial People's Hospital, Lanzhou, PR China - **Department of Endocrinology, Sichuan Fourth People's Hospital, Chengdu, PR China

Abstract

Objective: To investigate the effect of Wnt/β-catenin signalling and interleukin-6 (IL-6) in the pathogenesis of lupus nephritis (LN). 

Methods: A total of 24 patients with systemic lupus erythematosus (LE) who were treated in our hospital from May 2016 to July 2018 were randomly selected. Among them, 18 patients were included in the LN group (LE patients that also presented with LN), while the remainder (n=6) formed the non-LN group (LE patients that did not present with LN). Moreover, 24 normal healthy subjects were selected as the control group. Immunoglobulin expression in the serum immune complexes of the control group, LN group and non-LN group was observed. Human mesangial cells were cultured, and the proliferation of mesangial cells was detected using the CCK-8 method. The secretion of IL-6 after stimulation of glomerular mesangial cells by serum immunocomplexes in LN patients was detected by enzyme-linked immunosorbent assay (ELISA). The immune complexes prepared by serum and used before the treatment of LN patients included exogenous IL-6, anti-IL-6 and ani-IL-6+IL-6 (to stimulate human mesangial cells), while the expression of GSK3β, axin-1, β-catenin, and TCF-4 in the cytoplasm-as well as cyclin D1 in the nucleus-of various groups were also observed. The immune complexes prepared using patients’ serum after LN treatment were used to stimulate human mesangial cells at the same time and concentration while the expressions of [immune complex, exogenous IL-6, anti-IL-6, ani-IL-6+IL-6, immune complex + ani-IL-6+IL-6 (combination group)] GSK3β and β-catenin in various groups were observed. 

Results: The expression of IgG light chain, IgG heavy chain, IgA and IgM heavy chain in the LN group was significantly higher than that of the control and non-LN groups (P<0.05). At 0.25pg/mL, the proliferation of mesangial cells was significantly higher than 0.5pg/mL and 1pg/mL (P<0.05). Compared to the control group, the activity of glomerular mesangial cells in LN group increased significantly, while the activity of glomerular mesangial cells in LN group was significantly higher than in the non-LN group (P<0.05). Moreover, the IL-6 level in the LN group was significantly higher than that of control and non-LN groups (P<0.05); however, there was no significant difference in IL-6 level between the control and non-LN groups (P>0.05). Compared to the control group, GSK3β level was significantly higher in the immune complex group, while the expression levels of axin-1, β-catenin, TCF-4 and cyclin D1 were significantly lower (P<0.05). Compared to the immune complex group, the GSK3β level in the IL-6 group was significantly lower, while the expression levels of axin-1, β-catenin, TCF-4, cyclin D1 were significantly higher (P<0.05). Moreover, the expression levels of GSK3β and β-catenin in the immune complex group were significantly lower (P<0.05) compared to the control group. Furthermore, the expression level of β-catenin was significantly higher (P<0.05) compared to the immune complex group. 

Conclusion: The serum immune complexes of LN patients can inhibit Wnt/β-catenin signalling and promote the development of inflammatory response. Wnt/β-catenin signalling and IL-6 can interact to regulate immune complex-induced inflammatory response and then participate in the occurrence of LN.

Keywords

Wnt/β-catenin signalling, IL-6, lupus nephritis, pathogenesis.

DOI:

10.19193/0393-6384_2020_3_329