Repigmentation of Human Vitiligo Skin by NBUVB Is Controlled by Transcription of GLI1 and Activation of the β-Catenin Pathway in the Hair Follicle Bulge Stem Cells

Abstract

Vitiligo repigmentation is a complex process in which the melanocyte-depleted interfollicular epidermis is repopulated by melanocyte precursors from hair follicle bulge that proliferate, migrate, and differentiate into mature melanocytes on their way to the epidermis. The strongest stimulus for vitiligo repigmentation is narrow-band UVB (NBUVB), but how the hair follicle melanocyte precursors are activated by UV light has not been extensively studied. To better understand this process, we developed an application that combined laser capture microdissection and subsequent whole transcriptome RNA sequencing of hair follicle bulge melanocyte precursors and compared their gene signatures to that of regenerated mature epidermal melanocytes from NBUVB-treated vitiligo skin. Using this strategy, we found up-regulation of TNC, GJB6, and THBS1 in the hair follicle bulge melanocytes and of TYR in the epidermal melanocytes of the NBUVB-treated vitiligo skin. We validated these results by quantitative real-time-PCR using NBUVB-treated vitiligo skin and untreated normal skin. We also identified that GLI1, a candidate stem cell-associated gene, is significantly up-regulated in the melanocytes captured from NBUVB-treated vitiligo bulge compared with untreated vitiligo bulge. These signals are potential key players in the activation of bulge melanocyte precursors during vitiligo repigmentation.

Oxidative Stress–Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo

“…A recent study by Zhang et al (2019) reported that HMGB1 could be released from melanocytes exposed to UVB and promote the activation of ERK pathway in melanocytes in an autocrine way, which is consistent with the paracrine effects of HMGB1 on keratinocytes observed in our study. Notably, UVB phototherapy is a commonly used strategy for treating vitiligo by activating melanocyte stem cells and suppressing the function of autoreactive T cells (Bulat et al, 2011;Goldstein et al, 2018). However, the therapeutic effect of UVB phototherapy is limited, given that a considerable portion of patients with vitiligo is not responsive (Silpa-Archa et al, 2018), which may be due to the proinflammatory effects of UVB-induced HMGB1 on keratinocytes, according to our findings.…”

BMP4-Induced Differentiation of Human Hair Follicle Neural Crest Stem Cells into Precursor Melanocytes from Hair Follicle Bulge

“…Among the various pitfalls of NBUVB phototherapy as the main option for vitiligo treatment, one is the refractoriness and less responsiveness of repigmentation over time 3 .…”

Excimer laser/light treatment of alopecia areata: A systematic review and meta‐analyses

“…In addition, UV may directly affect the hair follicle cycling. A recent study showed that UVB light‐induced repigmentation of vitiligo patches by activating the β‐catenin pathway of hair‐follicle bulge stem cells 26 . As Wnt/β‐catenin signaling in dermal papilla cells is the canonical pathway inducing anagen phase and stimulating hair growth, 27,28 activation of the β‐catenin pathway by UVB light may stimulate hair regrowth of AA lesions.…”