A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH‐L1.

Lupus nephritis (LN), an autoimmune kidney disease caused by systemic lupus erythematosus (SLE), is the inflammation of the kidney. Although the treatment of LN is still a therapeutic challenge for many practitioners, the present study aims to provide a new insight for the treatment and management. The study aims to explore the effect of A20 on LN in relation to the nuclear factor‐kappa B (NF‐κB) signaling pathway. MRL/lpr mice were used as the LN mouse model. Next, A20, UCH‐L1, and NF‐κB expression in LN patients and MRL/lpr mice was determined. A20 was upregulated in podocytes to assess biological functions of A20 in LN. Furthermore, to further investigate the pivotal role of the NF‐κB pathway in LN, the NF‐κB pathway was blocked in podocytes. Next, UCH‐L1 was downregulated in MRL/lpr mice to assess biological functions of UCH‐L1 in LN. A20 was downregulated, whereas UCH‐L1 was upregulated in LN. Overexpressed A20 declined NF‐κB, UCH‐L1 expression, and the extent of p65 phosphorylation. A20 overexpression or UCH‐L1 inhibition increased expression of synaptoporin and nephrin but decreased desmin expression and ubiquitin accumulation level in podocytes. Moreover, A20 overexpression or UCH‐L1 inhibition increased the podocyte number but decreased protein level of cleaved caspase‐3, podocyte lesion improvement, decreased foot process width, glomerulus basement membrane, and foot process fusion rate. In addition, urine protein, blood urea nitrogen, serum creatinine, and ds‐DNA antibody levels decreased with elevated A20 or depleted UCH‐L1. Collectively, it could be concluded that A20 protects against podocyte injury in LN via UCH‐L1 by inactivating the NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]