The fibroblast hormone endotrophin is a biomarker of mortality in chronic diseases.
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Author
Genovese, FedericaBager, Cecilie
Frederiksen, Peder
Vazquez, Dario
Sand, Jannie Marie Bülow
Jenkins, R Gisli
Maher, Toby M
Stewart, Iain D
Molyneaux, Philip L
Fahy, William A
Wain, Louise V
Vestbo, Jørgen
Nanthakumar, Carmel
Shaker, Saher Burhan
Hoyer, Nils
Leeming, Diana Julie
George, Jacob
Trebicka, Jonel
Rasmussen, Daniel Guldager Kring
Hansen, Michael K
Cockwell, Paul
Kremer, Daan
Bakker, Stephan Jl
Selby, Nicholas M
Reese-Petersen, Alexander Lynge
González, Arantxa
Núñez, Julio
Rossing, Peter
Nissen, Neel I
Boisen, Mogens Karsbøl
Chen, Inna M
Zhao, Lei
Karsdal, Morten A
Schuppan, Detlef
Publication date
2024-06-11Subject
Endocrinology
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Fibrosis, driven by fibroblast activities, is an important contributor to morbidity and mortality in most chronic diseases. Endotrophin, a signaling molecule derived from processing of type VI collagen by highly activated fibroblasts, is involved in fibrotic tissue remodeling. Circulating levels of endotrophin have been associated with an increased risk of mortality in multiple chronic diseases. We conducted a systematic literature review collecting evidence from original papers published between 2012 and January 2023 that reported associations between circulating endotrophin (PRO-C6) and mortality. Cohorts with data available to the study authors were included in an Individual Patient Data (IPD) meta-analysis that evaluated the association of PRO-C6 with mortality (PROSPERO registration number: CRD42023340215) after adjustment for age, sex and BMI, where available. In the IPD meta-analysis including sixteen cohorts of patients with different non-communicable chronic diseases (NCCDs) (N=15,205) the estimated summary hazard ratio for 3-years all-cause mortality was 2.10 (95% CI 1.75-2.52) for a 2-fold increase in PRO-C6, with some heterogeneity observed between the studies (I2=70%). This meta-analysis is the first study documenting that fibroblast activities, as quantified by circulating endotrophin, are independently associated with mortality across a broad range of NCCDs. This indicates that, irrespective of disease, interstitial tissue remodeling, and consequently fibroblast activities, has a central role in adverse clinical outcomes, and should be considered with urgency from drug developers as a target to treat.Citation
Genovese F, Bager C, Frederiksen P, Vazquez D, Sand JMB, Jenkins RG, Maher TM, Stewart ID, Molyneaux PL, Fahy WA, Wain LV, Vestbo J, Nanthakumar C, Shaker SB, Hoyer N, Leeming DJ, George J, Trebicka J, Rasmussen DGK, Hansen MK, Cockwell P, Kremer D, Bakker SJ, Selby NM, Reese-Petersen AL, González A, Núñez J, Rossing P, Nissen NI, Boisen MK, Chen IM, Zhao L, Karsdal MA, Schuppan D. The fibroblast hormone Endotrophin is a biomarker of mortality in chronic diseases. Matrix Biol. 2024 Sep;132:1-9. doi: 10.1016/j.matbio.2024.06.003. Epub 2024 Jun 11.Type
ArticleAdditional Links
https://www.sciencedirect.com/journal/matrix-biologyPMID
38871093Journal
Matrix BiologyPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1016/j.matbio.2024.06.003