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
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.
