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Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease

Year: 2021
Type: article
Abstract: Chronic 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.
Source: iScience
DOI: 10.1016/j.isci.2021.103193
Authors: Cuiyan Xin, Jiahui Lei, Qian Wang, Yixia Yin, Xiaoqian Yang, Jose Alberto Moran Guerrero, Venkata Sabbisetti, Xiaoming Sun, Vishal S. Vaidya, Joseph V. Bonventre
Institutions: Brigham and Women's Hospital, Harvard University, Huazhong University of Science and Technology, First Affiliated Hospital of Zhengzhou University, Wuhan University of Technology, State Key Laboratory of Advanced Technology For Materials Synthesis and Processing
Language: English
Subfield: Nephrology
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,000
Funders: Pfizer, Brigham and Women's Hospital, Partners Healthcare, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
OpenAlex ID: W3203519640
FWCI: 1.169
Cites: 29
Cited by: 16
Related to: 10