Hua Zhou
The Shengjing Hospital of China Medical University, China
: J Kidney
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-?, Tnf-?) and profibrotic genes (TGF-?, ?-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
Hua Zhou completed her MD at China Medical University, PhD at Hamamatsu Medical University in Japan, and postdoctoral works at NIDDK. Prior to returning to China, she had conducted medical research at NIH for 9 years. Currently, she serves as the Vice Director of the Nephrology Department at Hospital of China Medical University, one of the top 20 medical universities in China. She has published 32 papers in prominent nephrology journals and has reached a citation number of 2300+. She also serves as an outstanding committee member of the Chinese Society of Renal Pharmacology and the Chinese Society of Renal Pathology.
E-mail: huazhou_cmu@163.com
