Repigmentation by combined narrow‑band ultraviolet B/adipose‑derived stem cell transplantation in the mouse model: Role of Nrf2/HO‑1‑mediated Ca<sup>2+</sup> homeostasis

Bian,Yuanyuan; Yu,Hao; Jin,Mingzhu; Gao,Xinghua

doi:10.3892/mmr.2021.12522

Repigmentation by combined narrow‑band ultraviolet B/adipose‑derived stem cell transplantation in the mouse model: Role of Nrf2/HO‑1‑mediated Ca²⁺ homeostasis

Authors:
- Yuanyuan Bian
- Hao Yu
- Mingzhu Jin
- Xinghua Gao
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Affiliations: Department of Dermatovenereal Disease, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Endocrinology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110016, P.R. China
Published online on: November 5, 2021 https://doi.org/10.3892/mmr.2021.12522
Article Number: 6
Copyright: © Bian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow‑band ultraviolet B (NB‑UVB) has emerged as the first choice of treatment for vitiligo, but long‑term exposure may have serious consequences. Recently, it was reported that adipose‑derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB‑UVB/ADSC‑transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca²⁺) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB‑UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3⁺, CD4⁺ and CD8⁺ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ‑induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca²⁺ homeostasis. Oxidative stress and Ca²⁺ unbalancing were improved after the mice were treated by NB‑UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB‑UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

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