Open AccessRNAi Silencing of HIF-1α Ameliorates Lupus Development in MRL/lpr Mice
Author(s) -
Wei Zhao,
Changhao Wu,
Lian-Ju Li,
YinGuang Fan,
HaiFeng Pan,
JinHui Tao,
RuiXue Leng,
DongQing Ye
Publication year - 2018
Publication title -
inflammation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.027
H-Index - 59
eISSN - 1573-2576
pISSN - 0360-3997
DOI - 10.1007/s10753-018-0815-6
Subject(s) - systemic lupus erythematosus , pathogenesis , immunology , gene silencing , autoimmunity , medicine , small hairpin rna , hypoxia inducible factors , cancer research , biology , antibody , cell culture , gene knockdown , gene , biochemistry , genetics , disease
Th17 cell and IL-17-mediated autoimmunity and inflammatory responses have been implicated in the development of organ damage in systemic lupus erythematosus (SLE), and new evidence suggests that hypoxia-inducible factor 1α (HIF-1α) enhances Th17 differentiation and promotes IL-17 production. However, the role of HIF-1α in the pathogenesis of lupus has not been examined. In this study, we silenced HIF-1α in vivo in a murine model of SLE to investigate whether lupus progression and the associated inflammatory pathways were affected by downregulating HIF-1α. Treatment with HIF1α-shRNA suppressed serum IL-17 level in MRL/lpr mice. Decreased anti-nucleosome antibody level, reduced urinary protein concentrations, ameliorated pathological damage, and remarkably reduced renal IgG and C3 depositions were observed in HIF1α-shRNA-treated group compared to those in the controls. Our results provide the first evidence for a role of HIF-1α in the pathogenesis of lupus and suggest a potential new therapeutic avenue for the treatment of lupus patients through reducing the HIF-1α level.