Mitochondria-Melanocyte cellular interactions: An emerging mechanism of vitiligo pathogenesis.

Mitochondria has emerged as a potential modulator of melanocyte function other than just meeting its cellular ATP demands. Mitochondrial DNA defects are now an established cause of maternal inheritance diseases. Recent cellular studies have highlighted the mitochondrial interaction with other cellular organelles that lead to disease conditions such as in Duchenne muscular dystrophy, where defective mitochondria was found in melanocytes of these patients. Vitiligo, a depigmentory ailment of the skin, is another such disorder whose pathogenesis is now found to be associated with mitochondria. The complete absence of melanocytes at the lesioned site in vitiligo is a fact; however, the precise mechanism of this destruction is still undefined. In this review we have tried to discuss and link the emerging facts of mitochondrial function or its inter- and intra-organellar communications in vitiligo pathogenesis. Mitochondrial close association with melanosomes, molecular involvement in melanocyte-keratinocyte communication and melanocyte survival are new paradigm of melanogenesis that could ultimately account for vitiligo. This definitely adds the new dimensions to our understanding of vitiligo, its management and designing of future mitochondrial targeted therapy for vitiligo.

A cross-sectional study to find association of VDR gene polymorphism with non-syndromic congenital ichthyosis and with vitamin D deficiency.

Though development of vitamin D deficiency and rickets in patients with congenital ichthyosis (CI) have recently been observed, yet exact cause of such association is not properly understood. To evaluate association between Vitamin D Receptor (VDR) polymorphism and CI, and to identify risk factors responsible for development of vitamin D deficiency in ichthyosis. In this cross-sectional study, detailed history of patients and controls was noted and certain biochemical investigations were made. Immunohistochemical staining of skin tissue was done for VDR expression in epidermal and dermal region of ichthyosis patients. VDR polymorphism was assessed in all participants. Ninety-six subjects, were recruited. Mean serum vitamin D was significantly lower among ichthyosis patients. Cdx-2 polymorphism was found to be significantly associated with ichthyosis (p = 0.009). Within the diseased group, Fok-1 (p = 0.035), age (p = 0.020) and alkaline phosphatase (ALP) (p = 0.007) emerged as factors which might be associated with vitamin D deficiency. Cdx2 polymorphism was significantly associated with CI patients. Also, association of Fok-1 polymorphism along with age and raised serum ALP levels emerged as potential factors for determining CI-related vitamin D deficiency.

Chemical induced pathognomonic features observed in human vitiligo are mediated through miR-2909 RNomics pathway.

BACKGROUND: Chemicals like Monobenzyl Ether of Hydroquinone (MBEH) and 4-Tertiary Butyl Phenol (4-TBP) have been widely recognized to induce clinical lesions that resemble vitiligo, but exact molecular pathway through which these chemicals initiate vitiligo is still far from clear. OBJECTIVES: Since vitiligo is widely considered as an autoimmune disease, this study was an attempt to understand miR-2909 RNomics in vitiligo pathogenesis using MBEH treated primary melanocytes as an archetype cellular model because MBEH causes pathological features indistinguishable from clinical vitiligo. METHODS: Primary melanocytes were treated with MBEH and 4-TBP and the role of miR-2909 RNomics at transcriptional and translational level was explored through qRT-PCR, western blot analysis, flow cytometry, immunocytochemistry, immunohistochemistry and in silico binding affinities. 4 mm punch biopsies were also obtained from lesional sites of vitiligo patients to validate the results observed in cell culture experiments. RESULTS: MBEH induced miR-2909 RNomics led to downregulation of MITF, TYR, TYRP1, and TYRP2 leading to decreased melanin synthesis which in turn is a characteristic trait of vitiligo. On the other hand, 4-TBP increased TGF-ß which also has the intrinsic capacity to downregulate MITF leading to decreased melanin synthesis and thereby initiation of vitiligo. CONCLUSION: Based upon our results we propose a molecular pathway which has the inherent capacity to resolve the mechanism through which these chemicals may induce vitiligo. This mechanism was also found to be involved in the lesional biopsies of vitiligo patients. These results could be exploited in better understanding the pathogenesis as well as in treatment of vitiligo.

Efficacy of Transplantation of Combination of Noncultured Dermal and Epidermal Cell Suspension vs Epidermal Cell Suspension Alone in Vitiligo: A Randomized Clinical Trial.

Importance: Surgical interventions, notably noncultured epidermal suspension (NCES), are the next line of treatment in patients with vitiligo who fail to respond to medical therapy. Noncultured epidermal suspension is usually performed in patients with vitiligo with duration of clinical stability (DS) of 12 months or longer because DS is a vital parameter in determining outcome of NCES. In this pilot study, we planned to assess the efficacy of a novel combination of noncultured epidermal cell suspension and noncultured dermal cell suspension (NCES and NDCS) in patients with vitiligo with shorter DS (3-6 months). Objective: To compare the efficacy of transplantation of NCES and NDCS vs NCES alone in patients with vitiligo with DS of 3 to 6 months. Design, Setting, and Participants: A single-center randomized clinical trial including 40 patients with focal, segmental, or generalized vitiligo with DS of 3 to 6 months or more than 12 months was carried out. Based on DS, 2 groups including 20 patients each were recruited (DS in group 1, 3 to 6 months; DS in group 2, more than 12 months). Each group was further randomized into 2 subgroups, A and B. Intervention: Patients in subgroups 1A and 2A underwent NCES alone, whereas patients in subgroups 1B and 2B underwent NCES and NDCS. Main Outcomes and Measures: Extent of repigmentation, color match, and pattern of repigmentation at 24 weeks. Results: Of the 40 study participants, mean (SD) age was 24.9 (4.0) years and 24 (60%) were women; in group 1 with DS for 3 to 6 months, more than 75% repigmentation at 24 weeks was observed in all 10 patients in subgroup 1B (NCES and NDCS) compared with 3 of 10 patients in subgroup 1A (NCES) (100% vs 30%, P = .003). In group 2 (DS > 12 months), the same was observed in 6 of 10 patients in subgroup 2A and 7 of 10 patients in subgroup 2B (NCES) (60% vs 70%, P > .99). The 2 groups and subgroups did not show any significant differences with respect to color matching and pattern of repigmentation. Conclusions and Relevance: Combination of NCES and NDCS resulted in excellent response in patients with vitiligo with shorter duration of clinical stability compared with NCES alone. This combination may be used early in the course of stable vitiligo without waiting for a period of 12 months or more since last clinical activity. Trial Registration: ClinicalTrials.gov identifier: NCT03013049.

Mitochondrial respiration is restricted by miR-2909 within human melanocytes.

Most of the cancer types in general and melanoma in particular exhibit mitochondrial dysfunction leading to the Warburg effect. Our present study stemmed from the observation that human A-375 and melanoma B16 cells displayed overexpression of a novel micro-RNA, miR-2909, shown in our earlier studies to be involved in aerobic glycolysis. Consequently, our study attempts to demonstrate the role of miR-2909 in the regulation of mitochondrial function within human melanocytes. Based upon such a study, we hypothesize that mitochondrial dysfunction observed in melanomas may result from deregulated miR-2909 expression within such cells.