A novel peptide 'T14' reflects age and photo-aging in human skin.

T14 is a 14mer peptide derived from the C-terminus of acetylcholinesterase (AChE). Once cleaved, it is independently bioactive of the parent molecule and enhances calcium influx in different cell types, in a range of scenarios: it binds to an allosteric site selectively on the alpha-7 receptor, where it modulates calcium influx and is thus a potential trophic agent, as already reported in a range of normal developmental scenarios. However, if inappropriately activated, this erstwhile beneficial effect converts to a toxic one, resulting in pathologies as disparate as Alzheimer's and various metastatic cancers. Given that epidermal keratinocyte cells have the same ectodermal origin as brain cells, as well as expressing AChE and the alpha-7 receptor, we have explored whether T14 plays a comparable role. Here we report that the T14 immunoreactivity is detectable in human keratinocytes with levels inversely related to age: this decrease is even more apparent with chronic photo-exposure and thus accelerated skin aging. We conclude that T14, an agent promoting cell growth and renewal in other parts of the body, also operates in skin, Moreover, monitoring of keratinocyte T14 levels might offer further insights into the now well reported link between degenerative diseases and epidermal cell profile.

Tight Junction barriers in human hair follicles - role of claudin-1.

Barrier function of hair follicles (HFs) is of great interest because they might be an entry port for allergens/pathogens, but could on the other hand be used for drug delivery or vaccination. Therefore we investigated tight junction (TJ) barrier function in human HFs. We show that there is a TJ barrier in the outermost living layer bordering to the environment from the infundibulum to the lower central part and between Henle's and Huxles layer of anagen HFs. In club hair typical for catagen and telogen HFs a TJ barrier is found surrounding the club. This demonstrates that there is a continuous TJ barrier along interfollicular epidermis and HFs in different phases of HF cycle. However, interestingly, in cell culture experiments we can show that barrier is less tight in HF keratinocytes compared to interfollicular keratinocytes. Knock-down of the TJ protein claudin-1, which we demonstrate here to be less expressed in HFs of lesional atopic dermatitis skin, results in impaired barrier function, decreased proliferation and increased apoptosis of hair keratinocytes. This is in line with a hair growth phenotype in claudin-1 deficient patients (NISCH syndrome) and corresponding knock-out mice and indicates an important role of claudin-1 in HF barrier function and growth.