A role for p75 neurotrophin receptor in the control of apoptosis-driven hair follicle regression

To examine the mechanisms that underlie the neurotrophin-induced, apoptosis -driven hair follicle involution (catagen), the expression and function of p75 neurotrophin receptor (p75NTR), which is implicated iu apoptosis contro l, were studied during spontaneous catagen development in murine skin. By R T-PCR, high steady-state p75NTR mRNA skin levels were found during the anag en-catagen transition of the hair follicle. By immunohistochemistry, p75NTR alone was strongly expressed in TUNEL+/Bcl2- keratinocytes of the regressi ng outer root sheath, but both p75NTR and TrkB and/or TrkC were expressed b y the nonregressing TUNEL/Bcl2+ secondary hair germ keratinocytes. To deter mine whether p75NTR is functionally involved in catagen control, spontaneou s catagen development was compared in vivo between p75NTR knockout (-/-) an d wild-type mice. There was significant catagen retardation in p75NTR knock out mice as compared to wild-type controls (P<0.05). Instead, transgenic mi ce-overexpressing NGF (promoter: K14) showed substantial acceleration of ca tagen (P<0.001). Although NGF, brain-derived neurotrophic factor (BDNF), an d neurotrophin 3 (NT-3) accelerated catagen in the organ-cultured skin of C 57BL/6 mice, these neurotrophins failed to promote catagen development in t he organ-cultured p75NTR null skin. These findings suggest that p75NTR sign aling is involved in the control of kerotinocyte apoptosis during catagen a nd that pharmacological manipulation of p75NTR signaling may prove useful f or the treatment of hair disorders that display premature entry into catage n.