Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone NZB/NZW F1 mice by modulating α-actinin-4 associated skeleton organization of podocytes

ABSTRACT: Glomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE). Podocytes can be injured in many forms of glomerular disease, characteristic changes are actin cytoskeleton reorganization of involved foot process. ACTN4, encodes α-actinin-4, an actin-binding and crosslinking protein localized to podocytes in renal glomerulus. Abnormal expression of α-actinin-4 in mice leads to proteinuria and podocyte damage. DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. Here, we found that DZ2002 could significantly ameliorate nephritis of lupus-prone mice. Our results showed that DZ2002 decreased the accumulation of α-actinin-4, inhibited expression of integrin-linked kinase and downstream phosphorylation of β1-integrin.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Xing Liu  

LAB HEAD: Hu Zhou

PROVIDER: PXD010059 | Pride | 2019-11-12

REPOSITORIES: Pride