Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo

Abstract

The regression phase of the hair cycle (catagen) is an apoptosis‐driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor β1 (TGF‐β1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF‐β1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF‐β1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF‐β1 null mice and age‐matched wild‐type littermates, and assessed the effects of TGF‐β1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF‐β1 —/— mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF‐β1 — /— mice displayed more Ki‐67‐positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF‐β1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratino‐cytes was reduced and the number of TUNEL + cells was increased in the TGF‐β1‐treated mice compared to controls. Double visualization of TGF‐β type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF‐β1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF‐βRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).—Foitzik, K., Lindner, G., Mueller‐Roever, S., Maurer, M., Botchkareva, N., Botchkarev, V., Handjiski, B., Metz, M., Hibino, T., Soma, T., Dotto, G. P., Paus, R. Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo. FASEB J. 14, 752–760 (2000)