Involvement of transforming growth factor-beta2 in catagen induction during the human hair cycle

The involvement of transforming growth factor-beta isoforms in the induction of the regressing phase (catagen) of human hair follicles were examined in vivo. In the growing phase (anagen), transforming growth factor-beta1 was detected at the hair cuticle and connective tissue sheath. Transforming growth factor-beta2 was restricted to the outermost cell layer of the outer root sheath. Transforming growth factor-beta3 was observed in the precortical hair matrix of anagen hair follicles. During the anagen-catagen transition phase, strong transforming growth factor-beta2 immunoreactivity appeared in the lower bulb matrix cells adjacent to the dermal papilla. In addition, transforming growth factor-beta2 and transforming growth factor-beta type II receptor were colocalized in the regressing epithelial strands, where terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive apoptotic cells were also found. Transforming growth factor-beta1 and transforming growth factor-beta3 were mostly negative in the strand. Using an organ culture system, we investigated whether transforming growth factor-beta2 and its antagonists affected the transition process. Elongation of hair was significantly suppressed by transforming growth factor-beta2. Next, a neutralizing antibody and fetuin, a potent transforming growth factor-beta antagonist was tested. In the presence of the antibody as well as fetuin, hair follicles were markedly elongated in a concentration-dependent manner. These results strongly suggest that transforming growth factor-beta2 plays an essential part in the induction of the catagen phase of the human hair cycle.