Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis

Abstract

Hairless (HR) is a nuclear protein with co-repressor activity that is highly expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss accompanied by the appearance of papules (atrichia with papular lesions) and similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) are overexpressed. Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine, leading us to investigate the mechanistic link between putrescine and HR. We show here that HR and putrescine form a negative regulatory network, since epidermal ODC expression is elevated when HR is decreased and vice versa. We also show that regulation of ODC by HR is dependent on the MYC superfamily of proteins, in particular MYC, MXI1 and MXD3. Furthermore, we found that elevated levels of putrescine lead to decreased HR expression but that the SSAT-TG phenotype is distinct from that of HR mutants. Transcriptional microarray analysis of putrescine-treated primary human keratinocytes demonstrated differential regulation of genes involved in protein-protein interactions, nucleotide binding, and transcription factor activity, suggesting that the putrescine-HR negative regulatory loop may have a large impact on epidermal homeostasis and hair follicle cycling.

Expression of decorin throughout the murine hair follicle cycle: hair cycle dependence and anagen phase prolongation

“…Skin specimens were obtained at days 0, 3, 5, 12 and 18 postdepilation (p.d. ), representing the telogen, anagen II, anagen IV, anagen VI and catagen phases, respectively . Three mice per time point were sacrificed, and dorsal skin samples (0.3 cm × 0.5 cm) harvested from the depilated areas were fixed in 4% paraformaldehyde in phosphate‐buffered saline (PBS) or immediately frozen in liquid nitrogen at −80°C.…”

Altered polyamine profiling in the hair of patients with androgenic alopecia and alopecia areata

“…Some studies have reported that polyamines play an important role in animal hair growth, that inhibition of polyamine synthesis regulates murine hair growth and that polyamines also help determine hair growth in sheep hair follicles . Recently, the correlation between hair loss and polyamines has received increasing attention . Polyamines are also associated with inflammation.…”

Constitutive activation of Stat3 in mouse epidermis is linked to hair deficiency and cytoskeletal network damage

“…HF cycling and hair growth are regulated in a myriad of ways via cytokines, growth factors, receptors and transcription factors (1,2). Uncontrolled signalling pathways resulting in overexpression and underexpression of HF proteins can cause severe hair growth abnormalities including hair loss (3,4).…”