Origin and Function of Myofibroblasts in Kidney Fibrosis
By Valerie S. LeBleu, G. Taduri, Joyce T. O’Connell, Ying-Hock Teng, V. Cooke, C. Woda, H. Sugimoto, Raghu Kalluri. Nature Medicine, 2013
1,227 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Nephrology
View Paper: https://www.semanticscholar.org/paper/44425a954877b971c6c0cdc95b88046d6385dba8
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Citations in the corpus
- Epithelial to Mesenchymal Transition induces cell cycle arrest and parenchymal damage in renal fibrosis (2015, neutral): “However, the precise contribution of EMT to the progression of kidney fibrosis remains a subject of debate 22–24 and only a minor population of α SMA + myofibroblasts are derived from TECs 4 .”
- Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Diminished Survival (2014, neutral): “PKT mice were crossed to R26-LSL-EYFP (purchased from Jackson Laboratory), aSMA-tk (LeBleu et al., 2013), and aSMA-RFP (LeBleu et al.”
- Single cell transcriptomes from human kidneys reveal the cellular identity of renal tumors (2018, neutral): “S1 to S19 Tables S1 to S12 References (10–46) Data S1 1 February 2018; accepted 2 July 2018 10.1126/science.aat1699 Young et al., Science 361, 594–599 (2018) 10 August 2018 6 of 6”
- Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis (2014, neutral): “Despite this, the contribution of pericytes to kidney fibrosis has recently been questioned (LeBleu et al., 2013).”
- Cellular and molecular mechanisms in kidney fibrosis. (2014, neutral): “Do other cells become myofibroblasts? A competing hypothesis about the origin of myofibroblasts in interstitial kidney disease has been that they arise from many disparate cell types, including fibroblasts, endothelium, epithelium, and leukocytes (41).”
- TGF-β1 Signaling and Tissue Fibrosis. (2018, background): “Deletion of the TGF-b receptor in fibroblasts, epithelial cells, or bone marrow cells results in abrogated fibrosis (Hoyles et al. 2011; Li et al. 2011; LeBleu et al. 2013).”
- TGF-β/Smad signaling in renal fibrosis (2015, background): “…that myofibroblasts may be derived from the resident fibroblasts, pericytes, bone marrow cells (e.g., fibrocytes), epithelial cells (Epithelial–mesenchymal transition, EMT), and endothelial cells (Endothelial–mesenchymal transition, EndMT) (Allison, 2013; LeBleu et al., 2013; Meng et al., 2014).”