Editors’ Picks from Experimental Dermatology

Epidermal suction blister gene expression study suggests an influence of non pigmentary genes for the regulation of ethnic skin color

Differences in visible skin pigmentation are a major determinant of skin color associated with ethnic background. The initial goal of this study (Yin et al, 2014) performed on epidermal extracts from individuals of Caucasian, Asian, and African ancestry, was to identify differentially expressed genes with a special focus on known pigment-related genes. However, only a few of them were found to be significantly differently expressed, such as FRZB, CDH12, SOX5 and KITLG. The major result was that the skin of Caucasians and Asians had highly similar gene expression patterns that differed significantly from the pattern of African skin. Interestingly, ADRA2C (α-2C adrenergic receptor) had a high expression level in African skin but low expression levels in Asian and Caucasian skin. α2-adrenoceptors are G-protein-coupled receptors that mediate many of the physiological effects of norepinephrine and epinephrine and they can regulate skin color in zebrafish (Ruuskanen et al, 2005). In humans, their so far unsuspected role in the regulation of pigmentation needs further investigation. NINL was found to be expressed at a significantly different level in Caucasian and Asian skin, in which comparable melanocyte populations and very similar melanin contents have been found. NINL has been shown to be involved in microtubule organization, and high levels of NINL expression cause lysosomes to disperse towards the cell periphery (Casenghi et al, 2005). Since melanosomes are lysosome-related organelles and their distribution is regulated by various cytoskeletal components, including microtubules, the authors hypothesize that the higher expression level of NINL in Asian skin might play a critical role in the different distribution patterns of melanosomes that result in visible skin color differences

Submitted by Alain Taieb, Bordeaux, France

References:

Yin L et al  (2014) Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry. Exp Dermatol. Oct;23(10):731-5. doi: 10.1111/exd.12518

Ruuskanen JO, Peitsaro N, Kaslin JV et al. J Neurochem 2005; 94: 1559-1569.

Casenghi M, Barr FA, Nigg EA. J Cell Sci 2005; 118: 5101-5108.

 

Bypassing epidermal immunity: A case of soft tissue infection in psoriatic skin

Psoriatic skin is characterized by an enhanced protective epidermal shield of antimicrobial peptides and proteins (AMPs). It is commonly believed that enhanced AMP levels in the skin from psoriasis patients, in contrast to those of atopic dermatitis patients, confer resistance to skin infections (Gambichlet et al, 2008; Ong et al, 2002; Howell et al, 2006).  However, if bypassed through penetrating injuries, epidermal AMPs are not sufficient to protect from bacterial soft tissue infection, as reported by Steinz et al (2014). This clinical observation goes against the paradigm that AMPs provide antimicrobial resistance and highlights that the route of infection and not local AMP deficiency may contribute to disturbed skin immunity. In addition, it remains to be determined whether topical psoriasis treatments, such as vitamin D derivatives or steroids, may inhibit the cutaneous immune system, resulting in enhanced infection susceptibility.

Submitted by Amanda S. MacLeod, Durham, NC, USA

References:

Gambichler T, Skrygan M, Tomi NS, Othlinghaus N, Brockmeyer NH, Altmeyer P, Kreuter A. (2008) Differential mRNA expression of antimicrobial peptides and proteins in atopic dermatitis as compared to psoriasis vulgaris and healthy skin. Int Arch Allergy Immunol. 47(1):17-24.

Ong PY1, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 10:347(15):1151-60.

Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, Leung DY (2006) Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 24(3):341-8.

Steinz K, Schubert S, Harder J, Gerdes S, Mrowietz U, Gläser R. (2014) Bacterial soft tissue infection in psoriasis despite induction of epidermal antimicrobial peptides. Exp Dermatol. 23(11):862-4

 

Stress and itch: Understanding the psychological aspects is important

The main complaint of patients suffering of atopic dermatitis is itch. Stress is understood to diminish the perception threshold of itch in this and many other diseases. However, it remained unclear which factors could explain this relationship.

Schut et al. wondered if certain coping strategies could be activated under stress. Coping can be defined as adaptable thoughts and behaviors intended to manage subjective demanding experiences. They investigated the role of coping as a possible mediating factor between stress and itch in patients with atopic dermatitis. Coping and itch were assessed by self-report measures, while stress was not only measured by a validated questionnaire, but also by a physiological stress marker, the post-awakening level of cortisol. Using a regression- and a mediation analysis, this study showed a relationship between perceived stress and itch, which was fully mediated by negative itch-related cognitions. More than 62% of the variance of itch intensity could be explained by negative itch-related cognitions.

These findings help to explain the positive effects of cognitive restructuring in the treatment of chronic itch. They provide a further scientific rationale for cognitive restructuring in the treatment of atopic dermatitis.

Submitted by Laurent Misery, Brest, France

Reference:

Schut C, Wiek U, Tews N, Gieler U, Deinzer R, Kupfer J. (2015) Coping as mediator of the relationship between stress and itch in patients with atopic dermatitis: a regression- and mediation analysis. Exp Dermatol 24(2):148-50

 

Hair Follicles’ Promise in Wound Healing

Jimenez et al.’s interesting essay, “Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice,” reviews experimental and clinical evidence regarding the potential benefits of using hair follicles in wound healing, and possible common pathways with hair cycling, including the role of molecular and cellular mechanisms.

The authors provide examples of the use of hair-related therapies to manage chronic wounds, such as cultured epidermal autografts obtained from the outer root sheath, and hair-bearing donor skin. Although the essay focuses on the influence of hair biology in wound healing, the points discussed are also applicable to therapies for depigmenting disorders and hair neogenesis for cicatricial alopecias, among others.

While the clinical evidence is still preliminary, in our opinion further research in hair biology may provide greatly needed new and effective wound healing therapies.

Submitted by Katherine L. Baquerizo Nole and Robert S. Kirsner, University of Miami, Miami, Florida, USA

References:

Jimenez F, Poblet E, Izeta A. (2015) Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice. Exp Dermatol  24(2):91-4.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s