MicroRNA-130b Ameliorates Murine Lupus Nephritis Through Targeting the Type I Interferon Pathway on Renal Mesangial Cells.
Type I interferon (IFN) is a critical pathogenic factor during the progression of lupus nephritis (LN). Although microRNAs (miRNAs) have been shown to control the IFN response in immune cells in LN, the role of miRNAs in resident renal cells remains unclear. We undertook this study to investigate the role of microRNA-130b (miR-130b) in the IFN pathway in renal cells as well as its therapeutic effect in LN.



Kidney tissues from patients and (NZB × NZW)F1 lupus-prone mice were collected for detecting miR-130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR-130b in the IFN pathway. We overexpressed miR-130b by administering miR-130b agomir in a mouse model of IFNα-accelerated LN to test its therapeutic efficacy.



Down-regulated miR-130b expression was observed in kidney tissues from patients and lupus-prone mice. Further analysis showed that underexpression of miR-130b correlated negatively with abnormal activation of the IFN response in LN patients. In vitro, overexpressing miR-130b suppressed signaling downstream from the type I IFN pathway in RMCs by targeting IFN regulatory factor 1 (IRF-1). The opposite effect was observed when endogenous miR-130b expression was inhibited. The inverse correlation between IRF1 and miR-130b levels was detected in renal biopsy samples from LN patients. More importantly, in vivo administration of miR-130b agomir reduced IFNα-accelerated progression of LN, with decreased proteinuria, lower levels of immune complex deposition, and lack of glomerular lesions.



MicroRNA-130b is a novel negative regulator of the type I IFN pathway in renal cells. Overexpression of miR-130b in vivo ameliorates IFNα-accelerated LN, providing potential novel strategies for therapeutic intervention in LN.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiao
X
Han
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan
Y
Wang
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaoyan
X
Zhang
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuting
Y
Qin
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bo
B
Qu
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lingling
L
Wu
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianyang
J
Ma
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenyuan
Z
Zhou
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jie
J
Qian
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Min
M
Dai
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuanjia
Y
Tang
University of Florida, Gainesville.
Edward K L
EK
Chan
Cincinnati Children's Hospital Medical Center and Cincinnati VA Medical Center, Cincinnati, Ohio.
John B
JB
Harley
Shanghai Institute of Rheumatology, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shiyu
S
Zhou
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Institute of Rheumatology, Shanghai Cancer Institute, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, and Shanghai Jiao Tong University School of Medicine, Shanghai, China, and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Nan
N
Shen
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D008181:Lupus Nephritis / Q000276:immunology*; D050527:Mesangial Cells / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D015398:Signal Transduction
D007370:Interferon Type I; C554019:MIRN130 microRNA, human; C582652:MIRN130 microRNA, mouse; D035683:MicroRNAs