Lesional skin in vitiligo exhibits delayed in vivo reepithelialization compared to the nonlesional skin

Abstract

Vitiligo, a common skin disorder, is characterized by the loss of functional melanocytes resulting in the depigmentation of skin. Previous studies have demonstrated molecular and architectural alterations in the epidermal keratinocytes upon loss of melanocytes. The physiological implications of these "altered" keratinocytes are yet not known. We investigated the wound healing efficiency of lesional vs nonlesional skin in 12 subjects with stable nonsegmental vitiligo using histological and ultrastructural evaluation of partial-thickness wounds. The wounds were examined 12 days postinjury, coinciding with the reepithelialization phase of healing marked primarily by keratinocyte migration and proliferation. This study demonstrated a significant difference in the reepithelialization potential between the lesional and nonlesional skin. While all 12 nonlesional wounds demonstrated considerable neoepidermis formation on the 12th day post wound, only four of the corresponding lesional samples showed comparable reepithelialization; the rest remaining in the inflammatory phase. Ultrastructural studies using transmission electron microscopy as well as immunohistochemical staining revealed a reduced number of desmosomes, shorter keratin tonofilaments and an increase in myofibroblast population in the dermis of lesional reepithelialized tissue compared to the nonlesional reepithelialized samples. This study implicates gross functional perturbations in the lesional skin during physiological wound healing in vitiligo, suggesting that the breakdown of keratinocytemelanocyte network results in delayed wound repair kinetics in the lesional skin when compared to patient-matched nonlesional skin.

Alterations of the pigmentation system in the aging process

“…Ultrastructural studies on the non‐lesional part of the vitiligo skin report altered keratinocytes, including the presence of extracellular granular material and vacuolar changes in basal keratinocytes associated with epidermal and dermal lymphocyte infiltrates (Moellmann et al, 1982; Hann et al., 1992). Lesional skin has a delayed wound repair (Gupta et al., 2020) and slow recovery kinetics compared with patient‐matched non‐lesional skin (Liu et al., 2010). Additionally, due to the selective loss of melanocytes, keratinocytes in the regions that lack pigment are vulnerable to environmental toxins (Lee et al., 2005).…”

Differential regulation of miR‐21‐5p delays wound healing of melanocyte‐deprived vitiligo skin by modulating the expression of tumor‐suppressors PDCD4 and Maspin

“…We chose the 14th day postwound (instead of the 12th day in our earlier study) to capture another time frame in the process of wound healing and investigate whether L re‐epithelialization finally manages to catch up with the NL skin. Though the L skin in this study exhibited significantly enhanced re‐epithelialization (Day 14) as compared to Day 12 (Gupta et al, 2020), the continued presence of spongiosis and hyperkeratosis (compared to Day 14 NL skin) indicated that the delay in wound healing persists even beyond the 12th day.…”

“…We chose the 14th day postwound (instead of the 12th day in our earlier study) to capture another time frame in the process of wound healing and investigate whether L reepithelialization finally manages to catch up with the NL skin. Though the L skin in this study exhibited significantly enhanced reepithelialization (Day 14) as compared to Day 12 (Gupta et al, 2020) (Banerjee & Sen, 2015;Schneider, 2012;Singhvi et al, 2018). For instance, miR-146a and miR-155 influence the inflammatory cascade by promoting the production of cytokines and growth factors necessary for the differentiation of monocytes into macrophages (Essandoh et al, 2016).…”

“…The re-epithelialization phase of cutaneous wound healing, characterized by the proliferation and migration of keratinocytes, culminates around 12-14 days post-wound (Nasir et al, 2019). Surprisingly, an earlier exploratory study carried out by our group had observed the L skin of individuals with vitiligo to exhibit delayed reepithelialization as compared to its paired NL skin (Gupta et al, 2020). Thus, we conducted this study to expand upon our earlier work and understand the molecular mechanisms underlying this delay.…”

“…Furthermore, the L epidermis is known to possess a completely distinct transcriptome than the NL skin (Singh et al, 2017; Yu et al, 2012). At the physiological level, these perturbations could be the reason behind the relative delay that has been observed in the re‐epithelialization of partial‐thickness wounds of L skin in vitiligo (Gupta et al, 2020).…”