Expression patterns of the glial cell line–derived neurotrophic factor, neurturin, their cognate receptors GFRα-1, GFRα-2, and a common signal transduction element c-Ret in the human skin hair follicles

Adly, Mohamed A.; Assaf, Hanan; Pertile, Paolo; Hussein, Mahmoud R.; Paus, Ralf

doi:10.1016/j.jaad.2007.10.014

Cited by 20 publications

(31 citation statements)

References 46 publications

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“…698 The involutionary stage, catagen, is quite short, lasting for less than 2 weeks in each hair follicle on the scalp. 708,709 It too is differentially expressed in different stages of the hair follicle cycle. Approximately 1% of scalp follicles are in the catagen phase at any time.…”

Section: The Normal Hair Cyclementioning

confidence: 99%

“…There is very little regional variation in the duration of catagen, although in some animals this period may be as short as 24 hours. 709 The levels of c-myc, c-myb, bax, and c-jun change immediately before or during early catagen, suggesting that they play a role in the induction of apoptosis. 685 In humans, the entry of follicles into catagen is a random process, in contrast to its synchronous onset in animals (molting).…”

Section: The Normal Hair Cyclementioning

confidence: 99%

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Diseases of cutaneous appendages

Weedon

2010

Weedon's Skin Pathology

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Section: The Normal Hair Cyclementioning

confidence: 99%

Section: The Normal Hair Cyclementioning

confidence: 99%

Diseases of cutaneous appendages

Weedon

2010

Weedon's Skin Pathology

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“…To assess the GDNF and GFRα‐1 immunoreactivity (IR) and alteration in staining intensity (SI) among different ages, semiquantitation of the immunostaining was carried out by calculating the immunoreactivity score (IR score) following Adly et al . (,b,c,d, ). The IR score was evaluated by multiplying the percentage of positive cells (PP%) and the staining intensity (SI).…”

Section: Methodsmentioning

confidence: 99%

“…In hair follicles organ culture, GDNF increased the number of the proliferating HF keratinocytes (Adly et al . ).…”

Section: Introductionmentioning

confidence: 97%

Age‐associated decrease in GDNF and its cognate receptor GFRα‐1 protein expression in human skin

Adly

Assaf

Hussein

2016

Int J Experimental Path

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Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations.

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“…Next, sections were incubated with avidin-biotin-alkaline phosphatase complex (Vecta-Stain Kits, Vector Laboratories Inc., Burlingame, CA, USA) diluted in TBS (1:100) for 30 min at room temperature. The alkaline phosphatase color reaction was developed by applying a staining protocol described earlier (Adly et al 2008a), using fast red tablets (SigmaAldrich Chemie GmbH, Steinheim, Germany). Finally, sections were counterstained with Meyer's hemalaum, covered with Kaiser glycerol (DAKO, Denmark) and stored at 4°C for microscopic examination and analysis.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Analysis of the expression pattern of the carrier protein transthyretin and its receptor megalin in the human scalp skin and hair follicles: hair cycle-associated changes

Adly

2010

Histochem Cell Biol

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Transthyretin is a serum and cerebrospinal fluid protein synthesized early in development by the liver, choroid plexus and several other tissues. It is a carrier protein for the antioxidant vitamins, retinol, and thyroid hormones. Transthyretin helps internalize thyroxine and retinol-binding protein into cells by binding to megalin, which is a multi-ligand receptor expressed on the luminal surface of various epithelia. We investigated the expression of transthyretin and its receptor megalin in the human skin; however, their expression pattern in the hair follicle is still to be elucidated. This study addresses this issue and tests the hypothesis that "the expression of transthyretin and megalin undergoes hair follicle cycle-dependent changes." A total of 50 normal human scalp skin biopsies were examined (healthy females, 53-62 years) using immunofluorescence staining methods and real-time PCR. In each case, 50 hair follicles were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Transthyretin and megalin were prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The concentrations of transthyretin and megalin were 0.12 and 0.03 Ul/ml, respectively, as indicated by PCR. The expression showed hair follicle cycle-associated changes i.e., strong expression during early and mature anagen, very weak expression during catagen and moderate expression during telogen. The expression values of these proteins in the anagen were statistically significantly higher than those of either catagen or telogen hair follicles (P ≤ 0.001). This study provides the first morphologic indication that transthyretin and megalin are variably expressed in the human scalp skin and hair follicles. It also reports variations in the expression of these proteins during hair follicle cycling. The clinical ramifications of these findings are open for further investigations.

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Expression patterns of the glial cell line–derived neurotrophic factor, neurturin, their cognate receptors GFRα-1, GFRα-2, and a common signal transduction element c-Ret in the human skin hair follicles

Cited by 20 publications

References 46 publications

Diseases of cutaneous appendages

Diseases of cutaneous appendages

Age‐associated decrease in GDNF and its cognate receptor GFRα‐1 protein expression in human skin

Analysis of the expression pattern of the carrier protein transthyretin and its receptor megalin in the human scalp skin and hair follicles: hair cycle-associated changes

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