Hua Zhou
The Shengjing Hospital of China Medical University, China
Title: The inhibition of renal miR-150 attenuated kidney injury in lupus nephritis by reducing inflammation and fibrosis
Biography
Biography: Hua Zhou
Abstract
We had previously reported that renal miR-150 correlates with chronicity in repeated kidney biopsies from lupus nephritis (LN) patients and that miR-150 agonist upregulates profibrotic and downregulates antifibrotic proteins in human podocyte, tubular, and mesangial cells. This suggests that miR-150 may be a target for treating renal fibrosis. We recently found that circular HLA-C might regulate miR-150 in LN patients with simple class IV. In this study, we subcutaneously injected locked nucleic acid (LNA)-anti-miR-150 (2mg/kg) in fcgr2b-/- mice, which is a spontaneous LN mouse model with different pathological classification. LNA-anti-miR-150 with FAM was seen in kidneys 6hr after injection. Renal miR-150 increased 2-fold in 40-week LN mice. LNA-anti-miR-150 (twice/week for 6-8 weeks) decreased renal miR-150 levels to around 30% of the diseased mice with scrambled LNA injection but did not show any other organ toxicity. Inhibition of renal miR-150 significantly attenuated proteinuria and kidney injury seen on PAS and MASSON. The levels of proinflammatory genes (Il6A, Ifn-γ, Tnf-α) and profibrotic genes (TGF-β, α-smooth muscle antibody, fibronectin) remarkably decrease and the expression of the anti-fibrotic gene (suppressor of cytokine signaling 1) increased. Lastly, we validated miR-150 in renal biopsies from new onset female LN patients with class III to class V (n=18) without treatment of steroid and immunosuppressant. We found renal miR-150 in LN patients increased compared with normal kidney tissue. We conclude that miR-150 inhibition protected LN from progression by downregulating proinflammatory and profibrotic genes and up-regulating anti-fibrotic genes. This suggested that LNA-anti-miR-150 may be a potential agent for treating renal fibrosis.