TGFB1 and varicose ulcer: Interestingly, based on a review of several studies reporting dermal fibroblast responsiveness to TGF-β1 in venous ulcers [120], it was suggested that slower proliferative response of fibroblasts throughout CVeD progression was associated with a decrease in TGF-βR2 expression (and consequent abnormalities in the downstream signaling pathway, i.e., failure of ulcer fibroblasts to phosphorylate Smad2/3 and p42/44 MAPK [121]), ultimately leading to senescence and poor ulcer healing.