UNASSIGNED: Wound healing in mammals is a fibrotic process. The mechanisms driving fibrotic (as opposed to regenerative) repair are poorly understood. Herein we report that therapeutic Wnt inhibition with topical application of small-molecule Wnt inhibitors can reduce @entity82 and promote regenerative cutaneous wound repair. In the naturally stented model of @entity2169 , we found that Wnt/b-catenin pathway is activated most notably in the dermis of the wound bed early (d 2) after injury and subsides to baseline levels by d10. Topical application of either of 2 mechanistically distinct small-molecule Wnt pathway inhibitors (a tankyrase inhibitor, @entity9949 , and the U.S. Food and Drug Administration-approved casein kinase activator, @entity29856 ) in C57Bl/6J @entity19 resulted in significantly increased rates of wound closure (72.3    14.7% with @entity9949 ; and 52.1    20.9% with @entity29856 ) compared with contralateral controls (38.1    23.0 and 40.4.  16.7%, respectively). Histologically, Wnt inhibition reduced @entity82 as measured by a-smooth muscle actin positive myofibroblasts and collagen type I a1 synthesis. Wnt inhibition also restored skin architecture including @entity4134 in ear wounds and @entity3161 with rete pegs in excisional wounds. Additionally, in @entity2169 Wnt inhibitor treatment enabled regeneration of auricular cartilage. Our study shows that pharmacologic Wnt inhibition holds therapeutic utility for regenerative repair of cutaneous wounds.-Bastakoty, D., Saraswati, S., Cates, J., Lee, E., Nanney, L. B., Young, P. P. Inhibition of Wnt/b-catenin pathway promotes regenerative repair of cutaneous and @entity1844 .

Inhibition of Wnt/b-catenin pathway promotes regenerative repair of cutaneous and XXXX .

@entity1844 :: ('MESH:D002357', 'Disease') :: ['cartilage injury'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity29856 :: ('MESH:C024631', 'Chemical') :: ['pyrvinium'] @entity3161 :: ('MESH:D020511', 'Disease') :: ['dermal-epidermal junction'] @entity4134 :: ('MESH:D000292', 'Disease') :: ['adnexal structures'] @entity9949 :: ('MESH:C544261', 'Chemical') :: ['XAV-939'] @entity2169 :: ('MESH:D004427', 'Disease') :: ['ear punch injury']
@entity1844 :: (MESH:D002357,Disease) :: ['cartilage injury']
