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Origin and function of myofibroblasts in kidney fibrosis
Open accessAbstract
Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)+ cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.
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Metadata
- Authors
- LeBleu, V. S., Taduri, G., O'Connell, J., Teng, Y., Cooke, V. G., Woda, C., Sugimoto, H., & Kalluri, R.
- Venue
- Nature Medicine
- Published
- 2013-06-30
- Volume
- 19
- Issue
- 8
- Pages
- 1047-1053
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2052092179
- Cited by
- 1,263
- References
- 4
- FWCI
- 74.03
- Type
- journal article
- Language
- en
- Open access
- green
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