Increased tenascin C and DKK1 in vitiligo: possible role of fibroblasts in acral and non-acral disease

Abstract

Recently, multiple culprits-in addition to melanocytes-have been implicated in the pathogenesis of vitiligo. Among those factors are fibroblasts. However, their exact role has not been clearly elucidated. The aim of the study was to evaluate the possible role played by fibroblasts in vitiligo via studying the expression Tenascin C and DKK1 in acral versus non-acral vitiligo lesions. This case-control study included 19 non-segmental vitiligo patients and ten controls. All patients were subjected to thorough clinical evaluation. Both Tenascin C and DKK1 were measured in lesional and peri-lesional skin of acral and non-acral lesions using ELISA technique. The measured levels of Tenascin C and DKK1 were significantly higher in the vitiligo group when compared to controls in all assessed sites (P < 0.05). Tenascin C was found to be significantly higher in lesional areas compared to peri-lesional ones only in the acral sites. DKK1 was significantly higher in lesional areas in all assessed sites (P < 0.05). The current work suggests a malfunction of fibroblasts in vitiligo, through demonstrating significant up-regulation of two melanogenesis inhibitory products (Tenascin C and DKK1) in patients compared to controls. Larger scale studies are warranted to detect the possible implications of such findings on vitiligo treatment.

Association between long noncoding RNA taurine‐upregulated gene 1 and microRNA‐377 in vitiligo

“…38 Senescence and malfunctioning of the dermal fibroblasts can reduce the secretion of cytokines and growth factors produced by fibroblasts that might result in death of melanocytes and progress of vitiligo. 39,40 The results of the present work also agree with the study done by Wang et al 41 who showed that miRNA-377 negatively regulates SOD1 and SOD2 protein expression, increasing p38MAPK phosphorylation and thioredoxin-interacting protein expression. Furthermore, they stated that the overexpression of miRNA-377 alone enhances oxidative stress in mesangial cells Figure 2 Comparative analysis between localized and generalized vitiligo regarding the expression of studied parameters (data were expressed as mean AE SD, P < 0.05 is statistically significant)…”

“…These factors influence the growth, pigmentation of melanocytes via the expression of melanin‐producing enzymes, and melanosome transfer 38 . Senescence and malfunctioning of the dermal fibroblasts can reduce the secretion of cytokines and growth factors produced by fibroblasts that might result in death of melanocytes and progress of vitiligo 39,40 …”

The possible role of Wnt/β‐catenin signalling in vitiligo treatment

“…DKK1 might inhibit recruitment of Axin to the plasma membrane, facilitating the phosphorylation of β‐catenin 19 . The expression of DKK1 is highly increased in vitiligo lesions and could play a role in vitiligo by suppression of Wnt signalling 20,21 …”

“…19 The expression of DKK1 is highly increased in vitiligo lesions and could play a role in vitiligo by suppression of Wnt signalling. 20,21 Tumour protein P53 (p53) is a negative regulator of the Wnt signalling. 4 The inhibitory effect of p53 on β-catenin is apparently mediated by the ubiquitin-proteasome system.…”

Novel immunological and genetic factors associated with vitiligo: A review

“…TNC acts as an anti-adhesive molecule (108). Since fibroblasts secrete TNC, fibroblasts may malfunction in vitiligo (109) and, therefore, TNC upregulation may impair the adhesion of melanocytes to surrounding keratinocytes and facilitate the process of melanocytorrhagy (109).…”