Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease
Summary: 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 rat...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221011615 |
| _version_ | 1818581382526402560 |
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| author | Cuiyan Xin Jiahui Lei Qian Wang Yixia Yin Xiaoqian Yang Jose Alberto Moran Guerrero Venkata Sabbisetti Xiaoming Sun Vishal S. Vaidya Joseph V. Bonventre |
| author_facet | Cuiyan Xin Jiahui Lei Qian Wang Yixia Yin Xiaoqian Yang Jose Alberto Moran Guerrero Venkata Sabbisetti Xiaoming Sun Vishal S. Vaidya Joseph V. Bonventre |
| author_sort | Cuiyan Xin |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-16T07:32:36Z |
| format | Article |
| id | doaj.art-0191900a45db43debe2d94491ac0a6ab |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T07:32:36Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0191900a45db43debe2d94491ac0a6ab2022-12-21T22:39:18ZengElsevieriScience2589-00422021-10-012410103193Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney diseaseCuiyan Xin0Jiahui Lei1Qian Wang2Yixia Yin3Xiaoqian Yang4Jose Alberto Moran Guerrero5Venkata Sabbisetti6Xiaoming Sun7Vishal S. Vaidya8Joseph V. Bonventre9Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Corresponding authorDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; The Second Department of General Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, ChinaDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, ChinaDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Corresponding authorDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221011615Biological sciencesBiochemistryMolecular biology |
| spellingShingle | Cuiyan Xin Jiahui Lei Qian Wang Yixia Yin Xiaoqian Yang Jose Alberto Moran Guerrero Venkata Sabbisetti Xiaoming Sun Vishal S. Vaidya Joseph V. Bonventre Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease iScience Biological sciences Biochemistry Molecular biology |
| title | Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease |
| title_full | Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease |
| title_fullStr | Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease |
| title_full_unstemmed | Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease |
| title_short | Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease |
| title_sort | therapeutic silencing of smoc2 prevents kidney function loss in mouse model of chronic kidney disease |
| topic | Biological sciences Biochemistry Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221011615 |
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