文章基本信息

标题：Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease
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作者：Cuiyan Xin ; Jiahui Lei ; Qian Wang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-19
DOI：10.1016/j.isci.2021.103193
语种：English
出版社：Elsevier
摘要：SummaryChronic kidney disease (CKD) is associated with substantial morbidity and mortality. We developed a mouse model that mimics human CKD with inflammation, extracellular matrix deposition, tubulointerstitial fibrosis, increased proteinuria, and associated reduction in glomerular filtration rate over time. Using this model, we show that genetic deficiency of SMOC2 or therapeutic silencing of SMOC2 with small interfering RNAs (siRNAs) after disease onset significantly ameliorates inflammation, fibrosis, and kidney function loss. Mechanistically, we found that SMOC2 promotes fibroblast to myofibroblast differentiation by activation of diverse cellular signaling pathways including MAPKs, Smad, and Akt. Thus, targeting SMOC2 therapeutically offers an approach to prevent fibrosis progression and CKD after injury.Graphical abstractDisplay OmittedHighlights•A mouse model of CKD that mimics human disease was generated•SMOC2 is significantly expressed in CKD and colocalizes with fibroblasts•Genetic and pharmacologic inhibition of SMOC2 prevents kidney function loss•SMOC2 activates multiple signaling pathways and autophagy in vitro and in vivoBiological sciences; Biochemistry; Molecular biology