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

Abstract

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.

Hair analysis as a biomonitor for toxicology, disease and health status

“…38 Additionally, Cu and Zn play vital roles in carcinogenesis. 41 Transthyretin has the capacity to bind with Zn, 42 thus could impact on cellular concentrations. 40 The transport protein transthyretin and its transmembrane receptor protein, Megalin, are multiligand endocytic receptors.…”

Increased retinol‐binding protein (RBP) 4 and anti‐RBP4 antibody in alopecia areata

“…We also identified elevated serum levels of TTR, a compound that facilitates the binding of the retinol/RBP and thyroxine/thyroxine‐binding protein complexes to cells, among subjects with AA, when compared with healthy controls 28,29 . TTR also assists internalization of RBP into the cells via megalin, a multiligand endocytic receptor for TTR expressed in various epithelia, including hair follicles 29 . Like RBP4, the expression of both TTR and megalin has also been shown to be hair cycle dependent 23,29 .…”

“…TTR also assists internalization of RBP into the cells via megalin, a multiligand endocytic receptor for TTR expressed in various epithelia, including hair follicles 29 . Like RBP4, the expression of both TTR and megalin has also been shown to be hair cycle dependent 23,29 . Furthermore, TTR exhibits strong immunoreactivity in the outer root sheath, hair matrix cells, dermal papillae and sebaceous glands in human scalp anagen VI hair follicles, with the basal and lower spinous layers of the epidermis displaying stronger immunoreactivity than the stratum granulosum and stratum corneum 29 .…”

Caveolin‐1 as a possible target in the treatment for acne

“…Megalin/LRP2 levels temporally vary during HF cycle. They are much higher in early anagen than in catagen or telogen . This means that the degree of the spatial HF synchronization should vary during HF cycle.…”

“…They are much higher in early anagen than in catagen or telogen. [30] This means that the degree of the spatial HF synchronization should vary during HF cycle. This effect can increase the area loaded with fatty acids extending it from a single HF to a spatially correlated group of HFs.…”