Journal article
IL-11 is a crucial determinant of cardiovascular fibrosis
S Schafer, S Viswanathan, AA Widjaja, WW Lim, A Moreno-Moral, DM DeLaughter, B Ng, G Patone, K Chow, E Khin, J Tan, SP Chothani, L Ye, OJL Rackham, NSJ Ko, NE Sahib, CJ Pua, NTG Zhen, C Xie, M Wang Show all
Nature | Published : 2017
DOI: 10.1038/nature24676
Abstract
Fibrosis is a common pathology in cardiovascular disease1. In the heart, fibrosis causes mechanical and electrical dysfunction1,2 and in the kidney, it predicts the onset of renal failure3. Transforming growth factor β1 (TGFβ1) is the principal pro-fibrotic factor4,5, but its inhibition is associated with side effects due to its pleiotropic roles6,7. We hypothesized that downstream effectors of TGFβ1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicity. Here we show, using integrated imaging-genomics analyses of primary human fibroblasts, that upregulation of interleukin-11 (IL-11) is the dominant transcriptional response to TGFβ1 exposure and required for its pr..
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Awarded by Howard Hughes Medical Institute
Funding Acknowledgements
We thank all patients for taking part in this research, which was performed with approval from the SingHealth Centralised IRB Review Board (CIRB; 2013/103/C). The research was supported by the National Medical Research Council (NMRC) Singapore STaR award (S.A.C.) (NMRC/STaR/0011/2012), the NMRC Centre Grant to the National Heart Centre Singapore (NHCS), Goh Foundation, Tanoto Foundation, NHLBI 5R01HL080494 (J.G.S., C.E.S.), HHMI (C.E.S.) and a grant from the Fondation Leducq (N.H., J.G.S., C.E.S., S.C.). We thank I. Kamer and R. Plehm, Max-Delbruck-Center for Molecular Medicine (MDC), for expert technical help with telemetry blood pressure measurements.