Your browser doesn't support javascript.
loading
Silica's silent threat: Contributing to skin fibrosis in systemic sclerosis by targeting the HDAC4/Smad2/3 pathway.
Tang, Bingsi; Shi, Yaqian; Zeng, Zhuotong; He, Xinglan; Yu, Jiangfan; Chai, Ke; Liu, Jiani; Liu, Licong; Zhan, Yi; Qiu, Xiangning; Tang, Rui; Xiao, Yangfan; Xiao, Rong.
Afiliación
  • Tang B; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Shi Y; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Zeng Z; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • He X; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Yu J; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Chai K; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Liu J; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Liu L; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Zhan Y; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Qiu X; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Tang R; Department of Rheumatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • Xiao Y; Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. Electronic address: xiaoyangfan@csu.edu.cn.
  • Xiao R; Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Key Laboratory of Medical Epigenetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. Electronic address: xiaorong65@csu.edu.cn.
Environ Pollut ; 355: 124194, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38782158
ABSTRACT
Nowadays, silica products are widely used in daily life, especially in skin applications, which inevitably increases the risk of silica exposure in general population. However, inadequate awareness of silica's potential hazards and lack of self-protection are of concern. Systemic sclerosis (SSc) is characterized by progressive tissue fibrosis under environmental and genetic interactions. Silica exposure is considered an important causative factor for SSc, but its pathogenesis remains unclear. Within this study, we showed that lower doses of silica significantly promoted the proliferation, migration, and activation of human skin fibroblasts (HSFs) within 24 h. Silica injected subcutaneously into mice induced and exacerbated skin fibrosis. Notably, silica increased histone deacetylase-4 (HDAC4) expression by inducing its DNA hypomethylation in normal HSFs. The elevated HDAC4 expression was also confirmed in SSc HSFs. Furthermore, HDAC4 was positively correlated with Smad2/3 phosphorylation and COL1, α-SMA, and CTGF expression. The HDAC4 inhibitor LMK235 mitigated silica-induced upregulation of these factors and alleviated skin fibrosis in SSc mice. Taken together, silica induces and exacerbates skin fibrosis in SSc patients by targeting the HDAC4/Smad2/3 pathway. Our findings provide new insights for evaluating the health hazards of silica exposure and identify HDAC4 as a potential interventional target for silica-induced SSc skin fibrosis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Piel / Fibrosis / Dióxido de Silicio / Proteína Smad2 / Proteína smad3 / Histona Desacetilasas Límite: Animals / Humans Idioma: En Revista: Environ Pollut Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Piel / Fibrosis / Dióxido de Silicio / Proteína Smad2 / Proteína smad3 / Histona Desacetilasas Límite: Animals / Humans Idioma: En Revista: Environ Pollut Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido