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Status |
Public on Feb 22, 2022 |
Title |
Myofibroblast YAP/TAZ activation is a key step in organ fibrogenesis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Fibrotic diseases account for nearly half of all deaths in the developed world. Despite its importance, the pathogenesis of fibrosis remains poorly understood. Recently, the two mechanosensitive transcription cofactors YAP and TAZ have emerged as important profibrotic regulators in multiple murine tissues. Despite this growing recognition, a number of important questions remain unanswered, including which cell types require YAP/TAZ activation for fibrosis to occur and the time course of this activation. Here, we present a detailed analysis of the role that myofibroblast YAP and TAZ play in organ fibrosis and the kinetics of their activation. Using analyses of cells, as well as multiple murine and human tissues, we demonstrated that myofibroblast YAP and TAZ were activated early after organ injury and that this activation was sustained. We further demonstrated the critical importance of myofibroblast YAP/TAZ in driving progressive scarring in the kidney, lung, and liver, using multiple transgenic models in which YAP and TAZ were either deleted or hyperactivated. Taken together, these data establish the importance of early injury-induced myofibroblast YAP and TAZ activation as a key event driving fibrosis in multiple organs. This information should help guide the development of new antifibrotic YAP/TAZ inhibition strategies.
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Overall design |
Analysis of 18 archival human transplant kidney biopsies with 12 normal control samples.
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Contributor(s) |
He X, Tolosa MF, Zhang T, Goru S, Severino L, Misra PS, McEvoy CM, Caldwell L, Szeto SG, Gao F, Chen X, Atin C, Ki V, Vukosa N, Hu C, Zhang J, Yip C, Krisova A, Wrana JL, Yuen DA |
Citation(s) |
35191398 |
Submission date |
Aug 02, 2019 |
Last update date |
Mar 09, 2022 |
Contact name |
Jeff Wrana |
Organization name |
Lunenfeld-Tanenbaum Research Institute
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Street address |
600 University Avenue
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City |
Toronto |
State/province |
Ontario |
ZIP/Postal code |
M5G 1X5 |
Country |
Canada |
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Platforms (2) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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Samples (30)
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Relations |
BioProject |
PRJNA558400 |
Supplementary file |
Size |
Download |
File type/resource |
GSE135327_AllRPMforGEO.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
Raw data are available in SRA |
Processed data are available on Series record |
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