TY  - JOUR
AB  - Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly associated with high morbidity and mortality. The medical need for effective antifibrotic therapies is thus very high. However, the extraordinarily high costs of drug development and the rare incidence of many fibrotic disorders hinder the development of targeted therapies for individual fibrotic diseases. A potential strategy to overcome this challenge is to target common mechanisms and core pathways that are of central pathophysiological relevance across different fibrotic diseases. The factors influencing susceptibility to and initiation of these diseases are often distinct, with disease-specific and organ-specific risk factors, triggers and sites of first injury. Fibrotic remodelling programmes with shared fibrotic signalling responses such as transforming growth factor-beta (TGF beta), platelet-derived growth factor (PDGF), WNT and hedgehog signalling drive disease progression in later stages of fibrotic diseases. The convergence towards shared responses has consequences for drug development as it might enable the development of general antifibrotic compounds that are effective across different disease entities and organs. Technological advances, including new models, single-cell technologies and gene editing, could provide new insights into the pathogenesis of fibrotic diseases and the development of drugs for their treatment.
AU  - Distler, J.H.W.*
AU  - Györfi, A.H.*
AU  - Ramanujam, M.*
AU  - Whitfield, M.L.*
AU  - Königshoff, M.
AU  - Lafyatis, R.*
C1  - 57317
C2  - 47685
CY  - 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
SP  - 705-730
TI  - Shared and distinct mechanisms of fibrosis.
JO  - Nat. Rev. Rheumatol.
VL  - 15
IS  - 12
PB  - Nature Publishing Group
PY  - 2019
SN  - 1759-4790
ER  - 

TY  - JOUR
AB  - Metabolomics is an exciting field in systems biology that provides a direct readout of the biochemical activities taking place within an individual at a particular point in time. Metabolite levels are influenced by many factors, including disease status, environment, medications, diet and, importantly, genetics. Thanks to their dynamic nature, metabolites are useful for diagnosis and prognosis, as well as for predicting and monitoring the efficacy of treatments. At the same time, the strong links between an individual's metabolic and genetic profiles enable the investigation of pathways that underlie changes in metabolite levels. Thus, for the field of metabolomics to yield its full potential, researchers need to take into account the genetic factors underlying the production of metabolites, and the potential role of these metabolites in disease processes. In this Review, the methodological aspects related to metabolomic profiling and any potential links between metabolomics and the genetics of some of the most common rheumatic diseases are described. Links between metabolomics, genetics and emerging fields such as the gut microbiome and proteomics are also discussed.
AU  - Menni, C.*
AU  - Zierer, J.
AU  - Valdes, A.M.*
AU  - Spector, T.D.*
C1  - 50866
C2  - 42757
CY  - New York
SP  - 174-181
TI  - Mixing omics: Combining genetics and metabolomics to study rheumatic diseases.
JO  - Nat. Rev. Rheumatol.
VL  - 13
IS  - 3
PB  - Nature Publishing Group
PY  - 2017
SN  - 1759-4790
ER  -