Nerve growth factor and its precursor differentially regulate hair cycle progression in mice.
Nerve growth factor (NGF) promotes proliferation via its high affinity receptor (TrkA). Its precursor proNGF promotes apoptosis via the pan-neurotrophin-receptor p75. Recently, we have identified NGF and p75 as important hair growth terminators. However, if proNGF is involved or if NGF can also promote hair growth via TrkA is unclear. By RT-PCR we found that NGF/proNGF mRNA levels peak during early anagen in murine back skin, whereas NGF/proNGF protein levels peak during catagen, indicating high turnover in early anagen and protein accumulation in catagen. By immunohistochemistry, NGF and TrkA are found in the proliferating compartments of the epidermis and hair follicle throughout the cycle. In contrast, strong proNGF is found in the highly differentiated inner root sheath and adjacent to the p75+ regressing epithelial strand in catagen. Commercial 7S NGF, which contains both NGF and proNGF, promotes anagen development in organ-cultured early anagen mouse skin, whereas it promotes catagen development in late anagen skin. Together, our findings suggest an anagen-promoting or anagen-supporting role for NGF/TrkA, and a catagen-promoting role for proNGF/p75 interactions. This has important implications for the future design of specific neurotrophin receptor ligands as novel pharmaceuticals in the modification of tissue remodeling processes such as hair growth or wound healing.
Peters
Eva M J
EM
Biomedical Research Center, Department of Internal Medicine, Psychosomatics, University-Medicine Berlin Charité, Berlin, Germany. eva.peters@charite.de
Hendrix
Sven
S
Gölz
Greta
G
Klapp
Burghard F
BF
Arck
Petra C
PC
Paus
Ralf
R
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006197:Hair / Q000378:metabolism* / Q000502:physiology; D018859:Hair Follicle / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D046509:Tissue Culture Techniques
D011498:Protein Precursors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor; D020917:Receptor, trkA