Biochemical and Biophysical Research Communications, Vol.522, No.3, 618-625, 2020
miR-150 inhibitor ameliorates adriamycin-induced focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome in USA. Its mechanisms remain unclear and the effective treatment lacks. We previously reported that upregulation of microRNA (miR)-150 in human podocytes increases profibrotic proteins and decreases anti-fibrotic suppressor of cytokine signaling 1 (SOCS1). We aimed to clarify whether miR-150 inhibitor can ameliorate glomerular injury and to identify its corresponding mechanisms in adriamycin-induced FSGS mice. We found that renal miR-150 increased in adriamycin-induced FSGS mice and FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) was absorbed by the animal kidneys 6 h after subcutaneous injection. The administration of LNA-anti-miR-150 (2 mg/kg BW twice weekly for 6 w) inhibited renal miR-150 levels without systemic toxicity. With renal miR-150 inhibition, proteinuria, hypoalbuminemia, and hyperlipemia were ameliorated in FSGS mice compared to the scrambled LNA. Meanwhile, the elevated profibrotic proteins and proinflammatory cytokines, decreased antifibrotic SOCS1, and the filtration of T cells in FSGS mice were reverted by LNA-anti-miR-150. Finally, we found that miR-150 most located on podocytes in renal biopsies of FSGS patients. We conclude that LNA-antimiR-150 might be a novel promising therapeutic agent for FSGS. The renal protective mechanisms might be mediated by anti-fibrosis and anti-inflammation as well as reducing infiltration of T cells in the kidney. (C) 2019 Published by Elsevier Inc.