Expression of truncated latent TGF-β-binding protein modulates TGF-β signaling

The study investigated the role of latent transforming growth factor-β-binding protein (LTBP) in modulating transforming growth factor-β (TGF-β) availability by using transgenic mice expressing a truncated form of LTBP-1. This truncated form lacked matrix-binding sequences but could still bind TGF-β. The overexpression of this mutated LTBP under the keratin 14-promoter led to a hair phenotype characterized by reduced keratinocyte proliferation, a shortened growth phase, and early onset of the catagen phase in the hair cycle. This was attributed to excess active TGF-β, as indicated by increased pSmad2/3-positive nuclei in the skin of transgenic mice. The findings suggested that the truncated LTBP-1 competed with the wild-type for binding to latent TGF-β, causing mis-localization and inappropriate activation of TGF-β, which prematurely initiated catagen. This highlighted the importance of LTBP interaction with TGF-β in its proper targeting and activation.