MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway

Bingsi Tang; Jiangfan Yu; Rui Tang; Xinglan He; Jiani Liu; Licong Liu; Zehong Song; Yaqian Shi; Zhuotong Zeng; Yi Zhan; Xiangning Qiu; Yangfan Xiao; Yan Ding; Rong Xiao

iScience (Aug 2024)

MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway

Bingsi Tang,
Jiangfan Yu,
Rui Tang,
Xinglan He,
Jiani Liu,
Licong Liu,
Zehong Song,
Yaqian Shi,
Zhuotong Zeng,
Yi Zhan,
Xiangning Qiu,
Yangfan Xiao,
Yan Ding,
Rong Xiao

Affiliations

Bingsi Tang: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Jiangfan Yu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Rui Tang: Department of Rheumatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Xinglan He: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Jiani Liu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Licong Liu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Zehong Song: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Yaqian Shi: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Zhuotong Zeng: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Yi Zhan: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Xiangning Qiu: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China
Yangfan Xiao: Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Corresponding author
Yan Ding: Department of Dermatology, Hainan Provincial Hospital of Skin Disease, Haikou, Hainan 570100, China; Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical College, Haikou, Hainan 570100, China; Corresponding author
Rong Xiao: Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China; Corresponding author

Journal volume & issue: Vol. 27, no. 8
p. 110483

Abstract

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Summary: Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3′UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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