UNASSIGNED: A role of Wnt signaling in @entity2074 , a fibroproliferative disease of the hand and fingers, has not been fully elucidated. We examined a large set of Wnt pathway components and signaling targets and found significant dysregulation of 41 Wnt-related genes in tissue from the Dupuytren nodules compared with @entity1 -matched control tissue. A large proportion of genes coding for Wnt proteins themselves was downregulated. However, both canonical Wnt targets and components of the noncanonical signaling pathway were upregulated. Immunohistochemical analysis revealed that protein expression of @entity59414 ( @entity59414 ), a known Wnt target, was increased in nodules compared with control tissue, but knockdown of @entity59414 using small interfering RNA (siRNA) in the Dupuytren myofibroblasts did not confirm a functional role. The protein expression of noncanonical pathway components @entity18297 and @entity26626 as well as noncanonical coreceptors @entity25997 and @entity42115 was increased in nodules. On the contrary, the strongest downregulated genes in this study were 4 antagonists of Wnt signaling ( @entity5741 , @entity34973 , @entity12393 , and @entity21124 ). Downregulation of these genes in the Dupuytren tissue was mimicked in  vitro by treating normal fibroblasts with @entity2533 ( @entity2533 ), suggesting cross talk between different profibrotic pathways. Furthermore, siRNA-mediated knockdown of these antagonists in normal fibroblasts led to increased nuclear translocation of Wnt target @entity3546 in response to @entity2533 treatment. In conclusion, we have shown extensive dysregulation of Wnt signaling in affected tissue from @entity2074 @entity1 . Components of both the canonical and the noncanonical pathways are upregulated, whereas endogenous antagonists are downregulated, possibly via interaction with other profibrotic pathways.

Wnt pathway in XXXX : connecting profibrotic signals.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity12393 :: ('6422', 'Gene') :: ['SFRP1'] @entity59414 :: ('8840', 'Gene') :: ['WISP1', 'Wnt1-inducible secreted protein 1'] @entity34973 :: ('2487', 'Gene') :: ['FRZB'] @entity3546 :: ('1499', 'Gene') :: ['b-catenin'] @entity42115 :: ('6259', 'Gene') :: ['Ryk'] @entity5741 :: ('22943', 'Gene') :: ['DKK1'] @entity2533 :: ('7040', 'Gene') :: ['TGF-b1', 'transforming growth factor b1'] @entity2074 :: ('MESH:D004387', 'Disease') :: ['Dupuytren disease'] @entity21124 :: ('11197', 'Gene') :: ['WIF1'] @entity18297 :: ('7474', 'Gene') :: ['Wnt5A'] @entity26626 :: ('57216', 'Gene') :: ['VANGL2'] @entity25997 :: ('4920', 'Gene') :: ['Ror2']
@entity2074 :: (MESH:D004387,Disease) :: ['Dupuytren disease']
