SBP1 contributes to mesangial proliferation and inflammation through mitochondrial respiration in glomerulus during IgA nephropathy
Junhyung Kim, Ji‐Hye Lee, Si‐Hyong Jang, Eun Young Lee, Mihye Lee, Samel Park, Jong‐Seok Moon
Abstract
Mesangial expansion and proliferation have been implicated in the pathogenesis of IgA nephropathy (IgAN). Mesangial cells in glomerulus are important contributors to commencement of IgAN. From minimal mesangial expansion to diffuse proliferation, the mesangial alteration is linked to clinical and pathological features of IgAN. Although selenium-binding protein 1 (SBP1) is associated with tissue injury, the roles of SBP1 in mesangial proliferation and inflammation in glomerulus during IgAN remains unclear. In the present study, we found that SBP1 gene levels were elevated in kidney tissues of patients with IgAN. Also, SBP1 protein levels were elevated in proliferative mesangial cells of glomerulus in kidney tissues from patients with IgAN. Urinary SBP1 protein levels were elevated in patients with IgAN. Elevated urinary SBP1 levels were positively correlated with segmental glomerulosclerosis of the Oxford classification related to mesangial proliferation in patients with IgAN. Over-expression of SBP1 induced cellular proliferation via mitochondrial respiration in human renal mesangial cells. Consistently, SBP1 knockdown and mitochondrial respiration inhibition suppressed cellular proliferation and induced mitochondrial oxidative stress in human renal mesangial cells. Furthermore, SBP1 induced pro-inflammatory phenotype by gene expression and production of pro-inflammatory cytokines and chemokines including IL-6, CXCL10, and CCL5 via NF-κB activation in human renal mesangial cells. These results suggest that SBP1 contributes to mesangial proliferation and inflammation via mitochondrial respiration during IgAN. • SBP1 levels are elevated in proliferative mesangial cells of glomerulus in IgAN. • Urinary SBP1 levels are correlated with segmental glomerulosclerosis. • SBP1 promotes mesangial proliferation via mitochondrial respiration. • Inhibition of mitochondrial respiration suppress mesangial proliferation. • SBP1 also induces mesangial pro-inflammatory phenotype.