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Canonical Wnt signalling as a key regulator of fibrogenesis – implications for targeted therapies?
Author(s) -
Dees Clara,
Distler Jörg H. W.
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12255
Subject(s) - wnt signaling pathway , morphogen , regulator , lrp5 , myofibroblast , microbiology and biotechnology , lrp6 , fibrosis , biology , signalling , cancer research , signal transduction , medicine , genetics , gene
Canonical Wnt signalling belongs to the so‐called morphogen pathways and plays essential roles in development and tissue homeostasis. Being such a crucial regulatory pathway, Wnt signalling is tightly controlled at different levels. However, uncontrolled activation of canonical Wnt signalling has been implicated into the pathogenesis of various human disorders. In the last years, aberrant Wnt signalling has been demonstrated in fibrotic diseases including systemic sclerosis ( SS c). In this review, we will discuss the current state of research on canonical Wnt signalling in SS c. Activation of canonical Wnt signalling induces fibroblast activation with subsequent myofibroblast differentiation and excessive collagen release resulting in tissue fibrosis. Genetic or pharmacological blockade of Wnt activation ameliorates experimental fibrosis in different preclinical models. These findings have direct translational implications because several small molecule inhibitors of Wnt signalling are currently evaluated in clinical trials and some already showed first promising results.