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Xin C, Lei J, Wang Q, et al. Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease. iScience. 2021;24(10):103193doi: 10.1016/j.isci.2021.103193.
Xin, C., Lei, J., Wang, Q., Yin, Y., Yang, X., Moran Guerrero, J. A., Sabbisetti, V., Sun, X., Vaidya, V. S., & Bonventre, J. V. (2021). Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease. iScience, 24(10), 103193. https://doi.org/10.1016/j.isci.2021.103193
Xin, Cuiyan, et al. "Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease." iScience vol. 24,10 (2021): 103193. doi: https://doi.org/10.1016/j.isci.2021.103193
Xin C, Lei J, Wang Q, Yin Y, Yang X, Moran Guerrero JA, Sabbisetti V, Sun X, Vaidya VS, Bonventre JV. Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease. iScience. 2021 Sep 29;24(10):103193. doi: 10.1016/j.isci.2021.103193. eCollection 2021 Oct 22. PMID: 34703992; PMCID: PMC8524153.
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iScience. 2021 Sep 29;24(10):103193. doi: 10.1016/j.isci.2021.103193. eCollection 2021 Oct 22.

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

iScience

Cuiyan Xin, Jiahui Lei, Qian Wang, Yixia Yin, Xiaoqian Yang, Jose Alberto Moran Guerrero, Venkata Sabbisetti, Xiaoming Sun, Vishal S Vaidya, Joseph V Bonventre

Affiliations

  1. Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  2. Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  3. The Second Department of General Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  4. State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

PMID: 34703992 PMCID: PMC8524153 DOI: 10.1016/j.isci.2021.103193

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.

© 2021 The Authors.

Keywords: Biochemistry; Biological sciences; Molecular biology

Conflict of interest statement

V.S.V. is an employee of Pfizer, Inc., co-inventor on SMOC2 patents assigned to Mass General Brigham (formerly known as Partners Healthcare) and is a co-founder of Mediar Therapeutics. J.V.B. is co-fo

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