Smad4-Dependent Desmoglein-4 Expression Contributes to Hair Follicle Integrity

The study from 15 years ago focused on the role of Smad4 in hair follicle integrity, particularly its involvement in the transcriptional regulation of desmoglein-4 (Dsg4), a protein essential for hair shaft differentiation and adhesion. Researchers found that Smad4, along with BMP mediators Smad1 and Smad5, is necessary for the maximal transactivation of Dsg4, as they bind to the Smad Binding Element (SBE) of the Dsg4 promoter. Mutation of the SBE or Smad4 deletion resulted in the downregulation of Dsg4 and subsequent hair follicle degeneration. The study used a mouse model with keratinocyte-specific deletion of Smad4 (K5.Smad4-/-), which developed alopecia due to degenerated hair follicles and hypertrophic sebaceous glands. The findings suggest that Smad4-dependent BMP signaling is crucial for Dsg4 expression and hair follicle integrity, and that the loss of Smad4 leads to hair loss and abnormal skin conditions. Future research was proposed to express a Dsg4 transgene in Smad4-deficient skin to further understand the relationship between Dsg4 loss and hair follicle degeneration. The work was supported by NIH grants and acknowledged contributions from various researchers.