@article{93a90c74f83a4763bf8311206eda65dd,
title = "Origin and function of myofibroblasts in kidney fibrosis",
abstract = "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.",
author = "Lebleu, {Valerie S.} and Gangadhar Taduri and Joyce O'Connell and Yingqi Teng and Cooke, {Vesselina G.} and Craig Woda and Hikaru Sugimoto and Raghu Kalluri",
note = "Funding Information: This study was supported by US National Institutes of Health (NIH) grants DK55001, DK81976, CA125550, CA155370, CA163191 and CA151925 (all to R.K.). R.K. is supported by the Cancer Prevention and Research Institute of Texas and the Metastasis Research Center at MD Anderson Cancer Center. V.S.L. was funded by the NIH Research Training Grant in Gastroenterology (2T32DK007760-11), V.G.C. was funded by the US National Research Service Award (NRSA) F32 Ruth Kirschstein Post-doctoral Fellowship from the NIH (5F32DK082119-02). H.S. was funded by the NIH Research Training Grant in Cardiovascular Biology (5T32HL007374-30). J.O. was funded by the US Department of Defense Breast Cancer Research Predoctoral Traineeship Award (W81XWH-09-1-0008). G.T. was funded by the International Society of Nephrology Fellowship. C.W. was funded by the NIH Research Training Grant in Pediatric Nephrology (T32DK007726). Pdgfrb-Cre mice were kindly provided by R. Adams, Max Planck Institute for Molecular Biomedicine. γGT-Cre mice were kindly provided by E. Neilson, Northwestern University. Tgfbr2flox/flox mice were kindly provided by H. Moses, Vanderbilt University.",
year = "2013",
month = aug,
doi = "10.1038/nm.3218",
language = "English (US)",
volume = "19",
pages = "1047--1053",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "8",
}