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. 2014 Feb;36(1):46-53.
doi: 10.1111/ics.12091. Epub 2013 Oct 15.

Protease activity, localization and inhibition in the human hair follicle

R K Bhogal  1 , P E Mouser  1 , C A Higgins  1 , G A Turner  2
Affiliations
Free PMC article

Protease activity, localization and inhibition in the human hair follicle

R K Bhogal et al. Int J Cosmet Sci. 2014 Feb.
Free PMC article

Abstract

Objective: In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials.

Methods: We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin.

Results: Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system.

Conclusion: These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding.

Keywords: exogen; follicle; hair growth; hair loss; hair shedding; hair treatment; proteases.

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Figures

Figure 1
Figure 1
Protease activity detected in material surrounding club root extracts and clipped hairs. Relative fluorescence units (RFU) were determined to be proportional to protease activity. Higher protease activity was found in material surrounding club root extracts compared with hair fibres.
Figure 2
Figure 2
(a) KLK5 staining at the level of the isthmus. (b) KLK5 staining around the mid-upper level of the hair follicle. Arrows show staining in the innermost layer of the outer root sheath. (c) KLK7 was observed in the cornified layers of the infundibulum and extended to the skin surface at which point the staining appeared more intense. (d) KLK7 staining at the level of the isthmus. Here, the staining appeared highest in the cells adjacent to the trichilemma. KLK14 staining around the telogen club (e) and in the hair follicle. Negative control section counterstained with haematoxylin (f).
Figure 3
Figure 3
Inhibition of trypsin activity by climbazole, Trichogen® and a combination of Trichogen® + climbazole.
See this image and copyright information in PMC

References

    1. Stenn KS, Parimoo S, Prouty SM. Growth of the hair follicle: a cycling and regenerating biological system. In: Chuong CM, editor. Molecular Basis of Epithelial Appendage Morphogenesis (Molecular Biology Intelligence Unit 1) Austin, TX: RG Landes Company; 1998. pp. 111–130.
    1. Tobin DJ, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev VA, Peters C, Paus R. The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am. J. Pathol. 2002;160:1807–1821. - PMC - PubMed
    1. Higgins CA, Westgate GE, Jahoda CA. Modulation in proteolytic activity is identified as a hallmark of exogen by transcriptional profiling of hair follicles. J. Invest. Dermatol. 2011;131:2349–2357. - PubMed
    1. Cash TF, Price VH, Savin RC. Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects. J. Am. Acad. Dermatol. 1993;29:568–575. - PubMed
    1. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol. Rev. 2001;81:449–494. - PubMed

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