Role of Ornithine Decarboxylase in Human Hair Follicles

Abstract

Ornithine decarboxylase (ODC), a pivotal enzyme in the polyamine biosynthesis, is known to be important in cell proliferation and differentiation. Animal studies have suggested that ODC plays an important role in the progression of hair follicle initiation and hair cycling. However, it is completely unclear whether this is of any relevance in human hair follicles.Accordingly, the purpose of the current study was to investigate the expression and effects of ODC in human hair follicles, and to provide further understanding about the functional roles of ODC in the human hair growth and hair cycle change. The expression of ODC in the human hair follicles and expression change of them were examined. And then, the effects of ODC on follicular keratinocyte (FKC) growth and proliferation/apoptosis related molecular expression were examined using α-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC and small interfering RNA (siRNA) technique. In addition, DFMO was used to check the effects of ODC on the human hair growth. Human hair follicles expressed ODC at mRNA and protein level. ODC immunoreactivity can be detected in the epithelium of human anagen hair follicles. During the transformation from anagen to catagen, ODC expression appeared to be down-regulated. DFMO inhibited the proliferation of FKC dose-dependently, and the level of phosphorylated extracellular signal-regulated kinase (P-ERK), phosphorylated protein kinase B (P-Akt), and B-cell CLL/lymphoma 2 (Bcl-2) were decreased and Bcl-2-associated X protein (Bax) was increased after treatment of DFMO. Gene transfection of ODC siRNA was markedly down-regulated the expression of ODC which resulted in suppression of FKC proliferation. Moreover, DFMO significantly inhibited the human hair growth and promoted apoptosis process in organ cultured human follicles. Taken together, these results indicate that ODC might be an important regulatory enzyme for human hair growth and the change of hair cycle.